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The amount of PsbO as well as the efficiency of PSII in psbo1 increased as the plants grew; however, it never reached the total PsbO level observed in the wild-type, suggesting that the p

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PsbO1 and PsbO2

Reiko Murakami1, Kentaro Ifuku1, Atsushi Takabayashi1, Toshiharu Shikanai2, Tsuyoshi Endo1 and Fumihiko Sato1

1 Division of Integrated Life Sciences, Graduate School of Biostudies, Kyoto University, Kyoto, Japan

2 Graduate School of Agriculture, Kyushu University, Higashiku, Fukuoka, Japan

In oxygenic photosynthesis, the multisubunit protein

complex photosystem II (PSII) uses light energy to

oxidize water and to form molecular oxygen [1–3]

Water oxidation occurs at a catalytic site of PSII that

contains four manganese atoms, and PSII contains

sev-eral extrinsic subunits that play important roles in

sta-bilizing the active manganese site One of these, the

nuclear-encoded PsbO protein in PSII, has a molecular

mass of approximately 26 kDa, although it has been

called extrinsic 33-kDa protein traditionally, and is

syn-thesized with a transit sequence that targets the protein

to the thylakoid lumen [4,5] PsbO is present in all

oxygen-evolving organisms It appears to play a central role in stabilization of the manganese cluster and is essential for efficient and stable oxygen evolution

To better understand the role of PsbO, mutants that lack the psbO gene have been established PsbO has been deleted using genetic methods in cyanobacteria [6,7] and in green algae [8], and such mutants have been maintained under heterotrophic conditions In contrast, no PsbO mutant has been obtained in higher plants due to the essential role of this protein in pho-tosynthesis Previously, however, we isolated an Ara-bidopsis mutant [9,10] with a defect in the psbO1 gene

Keywords

Arabidopsis thaliana; isoform; oxygen

evolution; psbO1; psbO2

Correspondence

T Endo

Division of Integrated Life Sciences,

Graduate School of Biostudies, Kyoto

University, Kyoto 606–8502, Japan

Fax: +81 75 7536398

Tel: +81 75 7536381

E-mail: tuendo@kais.kyoto-u.ac.jp

(Received 24 December 2004, revised 17

February 2005, accepted 1 March 2005)

doi:10.1111/j.1742-4658.2005.04636.x

PsbO protein is an extrinsic subunit of photosystem II (PSII) and has been proposed to play a central role in stabilization of the catalytic manganese cluster Arabidopsis thaliana has two psbO genes that express two PsbO proteins; PsbO1 and PsbO2 We reported previously that a mutant plant that lacked PsbO1 (psbo1) showed considerable growth retardation despite the presence of PsbO2 [Murakami, R., Ifuku, K., Takabayashi, A., Shika-nai, T., Endo, T., and Sato, F (2002) FEBS Lett 523, 138–142] In the pre-sent study, we characterized the functional differences between PsbO1 and PsbO2 We found that PsbO1 is the major isoform in the wild-type, and the amount of PsbO2 in psbo1 was significantly less than the total amount

of PsbO in the wild-type The amount of PsbO as well as the efficiency of PSII in psbo1 increased as the plants grew; however, it never reached the total PsbO level observed in the wild-type, suggesting that the poor activity

of PSII in psbo1 was caused by a shortage of PsbO In addition, an in vitro reconstitution experiment using recombinant PsbOs and urea-washed PSII particles showed that oxygen evolution was better recovered by PsbO1 than

by PsbO2 Further analysis using chimeric and mutated PsbOs suggested that the amino acid changes Val186fi Ser, Leu246fi Ile, and Val204fi Ile could explain the functional difference between the two PsbOs Therefore we concluded that both the lower expression level and the inferior functionality of PsbO2 are responsible for the phenotype observed in psbo1

Abbreviations

Fm, maximum fluorescence yield at closed PSII centers; F0, minimum fluorescence yield at open PSII centers; Fv, Fm) F 0 ; PSII,

photosystem II.

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(psbo1), as PsbO proteins in Arabidopsis are encoded

by two genes, psbO1 and psbO2 [11] On the other

hand, many other plant species have only one psbO

gene The second gene in Arabidopsis would be a

unique result of a duplication of the genome and

chro-mosomes some 28–48 million years ago, before the

divergence of Arabidopsis from Brassica about 14–24

million years ago [12,13]

Our previous analysis showed that psbo1 exhibited

weak photosynthetic activity and considerable growth

retardation compared with the wild-type [10] This

observation raised the question of why the psbO2 gene

could not complement the defect in the psbO1 gene,

since PsbO1 and PsbO2 are highly homologous with

regard to the primary structure

In this study, we characterized the differences in the

accumulation and biochemical activity of these

iso-forms to clarify their functional differences A detailed

immunoblot analysis using the mutant, psbo1, and the

wild-type showed that a lower level of PsbO2 would

limit the photosynthetic activity Additional in vitro

experiments with urea-washed PSII particles

reconsti-tuted with PsbOs revealed that oxygen-evolution was

better recovered by PsbO1 than by PsbO2, though the

two isoforms had a similar binding affinity for the

PSII particles These results showed that the

differ-ences in both biochemical activity and the level of

accumulation were responsible for the poor

photosyn-thetic activity in psbo1

We further dissected the functional differences

between PsbO1 and PsbO2, as these isoforms have

quite a similar primary structure, and differ at only 11

amino acids A previous investigation [5] pointed out

the importance of Cys at positions 29 and 52 of

mature PsbO1 for forming a disulfide bridge [14,15],

and Val at position 148 for producing a b-sheet [16],

as well as carboxylic residues that have been reported

to be involved in the interaction between PsbO and

PSII [17,18] Moreover, these amino acid residues are

conserved in PsbO2 In addition, the predictions

regarding the structures of Arabidopsis PsbO1 and

PsbO2 based on PSII of Thermosynechococcus

elonga-tus [19] (protein data bank accession number 1S5L)

were similar Thus, to identify the amino acids

respon-sible for the poor oxygen-evolving activity of PsbO2,

we prepared chimeric proteins derived from PsbO1

and PsbO2 Further, site-directed mutagenesis showed

that the replacement of Val186 of mature PsbO1

with Ser and of Leu246 with Ile decreased the

oxygen-evolving activity, whereas substitution of Val-204 with

Ile increased the oxygen-evolving activity Based on

these results, we discuss the physiological role of the

duplicated PsbO in Arabidopsis

Results

PsbO isoform level and the efficiency of PSII

To understand the reason for the loss of photosyn-thetic activity in psbo1, we measured the protein levels

of PsbOs and the photosynthetic activity in mutant and wild-type plants Whereas the wild-type plants maintained strong photosynthetic activity throughout their growth, psbo1 plants showed a gradual increase

in electron transport activity, represented by the chlo-rophyll fluorescence parameter, Fv⁄ Fm (the maximum photochemical efficiency in PSII) [20,21], as they grew (Fig 1)

SDS⁄ PAGE, since PsbO1 migrated more slowly than PsbO2 [10] Immunoblot analysis showed that the major isoform in the wild-type was PsbO1, which com-prised about 90% of the total amount of PsbO based

on densitometry of the immunoblot membranes (Fig 2A) The amount of PsbO2 was much greater in psbo1than in the wild-type (Fig 2A,B), indicating that the expression of psbO2 was activated in a compensa-tory manner At an early growth stage, the PsbO2 level

in psbo1 accounted for 40% of the total in the wild-type The amount of PsbO2 increased considerably in mature psbo1, and reached about 70% of the total

in the wild-type This change in the level of PsbO2 coincided with the change in Fv⁄ Fm in immature and mature psbo1 plants; i.e 0.54 ± 0.05 and 0.68 ± 0.03, respectively The accumulation of PsbO2 in mature plants clearly led to more efficient PSII

Similarly, immunoblot analysis of other PSII pro-teins, PsbA and PsbP, showed that the amounts of

0.3 0.4 0.5 0.6 0.7 0.8 0.9

days after germination

wild-type

psbo1

Fig 1 Potential quantum yield of PSII (Fv⁄ F m ) in leaves of the wild-type (r) and psbo1 (h) during the course of plant growth Values represent averages and standard deviations for 10–15 plants.

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PsbA and PsbP were also smaller in psbo1 than in the

wild-type (Fig 2A,B), whereas the levels of these

pro-teins also increased as psbo1 grew As PsbO stabilizes

the manganese cluster and PSII core, and it has often

been reported that PsbO deficiency affects the amount

of PsbA and PsbP [22–24], it is very likely that the

amount of PsbOs limits the amounts of PsbA and

PsbP These results suggest that the amount of PsbOs

in psbo1 is the critical limiting factor for

photosyn-thesis and growth

Biochemical activities of PsbO1 and PsbO2

in oxygen evolution

As it was clear that the shortage of PsbOs in psbo1 is

the critical limiting factor for photosynthesis, we

car-ried out in vitro experiments using recombinant PsbOs

and urea-washed PSII particles from spinach to clarify

the qualitative differences between PsbO1 and PsbO2

ArabidopsisPsbO has been reported to be able to bind

urea-washed PSII particles of spinach and to restore

the oxygen-evolving activity as effectively as spinach

PsbO [16,25] We carried out reconstitution procedures

according to their methods First, we examined the oxygen-evolving activity as a function of the PsbOs⁄ PSII ratio in the assay medium (Fig 3A) The maxi-mum activity with PsbO2 was about 80% of that with PsbO1, whereas the maximum oxygen-evolving activity reconstituted with both PsbO1 and PsbO2 was achieved at about 2 PsbOs⁄ PSII The restoration curve obtained with our recombinant PsbOs closely resem-bled that for spinach PsbO and Arabidopsis PsbO1 reported by Betts et al [25] PsbO1 and PsbO2 also showed a similar affinity for urea-washed PSII parti-cles (Fig 3B,C); the binding of both PsbOs with urea-washed PSII particles was saturated at about 2 PsbOs⁄ PSII, like the oxygen-evolving activity

Competition analysis of PsbO1 and PsbO2

To confirm that the two PsbOs have a similar binding affinity, the competition between them for binding sites

on PSII particles was analyzed Increasingly larger amounts of an equimolar mixture of PsbO1 and PsbO2 were incubated with urea-washed PSII particles (Fig 4A,B), and the relative amounts of bound-PsbO1

wild-type young

wild-type mature

psbo1

young

psbo1

mature

PsbO PsbA PsbP

140 120 100 80 60 40 20 0

PsbA

PsbP

wild-type M Y

psbo1

M Y

wild-type M Y

psbo1

M Y

CBB-staining

PsbO1 PsbO2

A

B

Fig 2 Protein analysis by SDS ⁄ PAGE

(15%) (A) Coomassie brilliant blue-staining

and immunoblot analysis with polyclonal

antibodies against spinach PsbO, PsbP and

PsbA Antibodies against PsbO detect two

signals with slightly different migrations,

upper band; PsbO1, lower band; PsbO2.

Thylakoid membranes were loaded on a

chlorophyll basis; equivalent to 5 lg of

chlo-rophyll for Coomassie brilliant blue-staining

and 1 lg for immunoblot analysis The

arrow shows PsbOs in Coomassie brilliant

blue-staining Y, young plants (leaf size,

about 0.5 cm); M, mature plants (leaf size,

about 2.5 cm) (B) The relationship between

the accumulation of PsbO (black), PsbP

(mid-grey) and PsbA (light grey) The protein

level was quantified by densitometry Values

are relative to the protein level in the young

wild-type (100%) Standard deviations were

calculated from three measurements.

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and bound-PsbO2 with urea-washed PSII particles

were quantified by the densitometry of Coomassie

bril-liant blue-stained proteins on a SDS⁄ PAGE plate As

PsbO1 migrated more slowly than PsbO2, the two

could be distinguished in the binding analysis

[10,26–28] Urea-washed PSII particles incubated with

two moles of PsbOs per mole of PSII particles (one

mole of each protein added, 1 : 1) had similar amounts

of PsbO1 and PsbO2 (approximately PsbO1⁄ PsbO2 ¼

51 : 49) The oxygen-evolving activity with a mixture

of one mole each of PsbO1 and PsbO2 was higher than that with four moles of PsbO2, but lower than that with four moles of PsbO1 Although the differ-ence was small, the same results were obtained consis-tently As the levels of both proteins were saturated at about 2 PsbOs⁄ PSII, we added an excessive amount of PsbOs per PSII (two moles of each protein, 2 : 2) The two proteins bound equally with urea-washed PSII (approximately 50 : 50) and the oxygen-evolving activ-ity was as high as the sample; 1 : 1 These results sug-gested that the two proteins had a similar affinity for urea-washed PSII

Next, we examined the effect of increasing the propor-tion of PsbO1 on the reconstitupropor-tion of PSII The ratio of PsbO1 to total PsbOs bound with urea-washed PSII particles and the oxygen-evolving activity demonstrated equal competition between PsbO1 and PsbO2 for PSII particles (Fig 4C) These competition analyses were consistent with the analysis of the reconstitution with PsbO1 and PsbO2, in terms of similar binding affinity

Chimeric PsbOs and surface charge

To examine which amino acid of PsbO2 is responsible for the poor oxygen-evolving activity, we prepared chi-meric proteins with PsbO1 and PsbO2 in Escherichia coli (Fig 5A) For example, the chimeric protein PsbO1-1-2 has the N-terminal and middle parts of PsbO1 combined to the C-terminus of PsbO2 Each of the parts contains about 80 amino acids, and, respect-ively, has three, five and three amino acid replacements between PsbO1 and PsbO2

SDS⁄ PAGE analysis of chimeric PsbOs showed that PsbO1-1-2 and PsbO2-1-1 migrated as slowly as PsbO1, and only PsbO1-2-1 migrated as PsbO2 did (Fig 5B) Anion-exchange chromatography was also performed, as PsbO1 was eluted at a higher NaCl

PsbO1

PsbO2

100

80

60

40

20

0

untreated PSIIurea-w

ashed PSII

0.5 1 2 4 0.5 1 2 4

PsbO1 PsbO2

140

120

100

80

60

40

20

0

PsbO1

PsbO2

A

B

C

Fig 3 The oxygen-evolving activity of urea-washed PSII reconstitu-ted with PsbO1 and PsbO2 and the binding affinity for urea-washed PSII of PsbO1 and PsbO2 (A) The relative oxygen-evolving activity

of urea-washed PSII reconstituted with PsbO1 (r) and PsbO2 (h) The maximum rate of oxygen evolution (100%) equals the rate measured for untreated PSII minus that for urea-washed PSII (B) Coomassie brilliant blue-staining Urea-washed PSII reconstituted with PsbO1 and PsbO2 were separated on SDS ⁄ PAGE (15%) An amount equivalent to 2 lg of chlorophyll was loaded in each lane The arrow shows PsbOs in Coomassie brilliant blue-staining (C) Quantification of PsbO1 (r) and PsbO2 (h) bound to urea-washed PSII particles Values quantified by densitometry were plotted against PsbOs added per PSII Values are relative to the untreated PSII (100%) Standard deviations were calculated from five meas-urements.

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concentration than was PsbO2 PsbO1-2-1 again

showed a chromatographic elution profile similar to

PsbO2, whereas the profiles of other chimeric proteins

were similar to that of PsbO1 (data not shown) In

fact, these results were consistent with the theoretical

pI values; the theoretical pI values of PsbO1, PsbO1-1-2 and PsbO2-1-1 were calculated to be 4.96 (calculated molecular mass, 26565 Da), 4.95 (26567 Da) and 4.96 (26579 Da), respectively, and those of PsbO2 and PsbO1-2-1 were calculated to be 5.05 (26571 Da) and 5.06 (26555 Da), respectively (to compute pI⁄ Mw, http://kr.expasy.org) These results suggest that, in terms of surface charge, PsbO1-2-1 was similar to PsbO2 and the other chimeric PsbOs were similar to PsbO1

PsbO1 PsbO2

PsbO1-1-2 PsbO2-1-1 PsbO1-2-1

A

B

C

Fig 5 Oxygen-evolving activity of chimeric proteins derived from PsbO1 and PsbO2 (A) A model of the chimeric PsbOs In chimeric PsbOs, a part of PsbO1 (C-terminus, middle and N-terminus) was replaced by a corresponding part of PsbO2 Each of the parts con-tains about 80 amino acids, and, respectively, has three, five and three amino acid replacements between PsbO1 and PsbO2 (B) Coomassie brilliant blue-staining on SDS ⁄ PAGE (15%) of PsbO1, PsbO2 and chimeric PsbOs They were expressed using a pET-sys-tem in Escherichia coli and purified by anion-exchange chromato-graphy Protein (0.5 lg) was loaded in each lane (C) Oxygen-evol-ving activities of urea-washed PSII reconstituted with PsbO1, PsbO2 and chimeric PsbOs The maximum rate of oxygen evolu-tion (100%) equals the rate measured for untreated PSII minus that for urea-washed PSII.

untreated

PSII

urea-washed

PSII

PsbO

PsbO2

(1:1)

(2:2)

100

0 0.2 0.4 0.6 0.8 1

100 80 60 40 20 0 120

A

B

C

Fig 4 Competition of PsbO1 and PsbO2 for the reconstitution of

PSII (A) Reconstitution of PSII with an equimolar mixture of PsbO1

and PsbO2 Reconstituted PSII particles were separated on a 15%

SDS ⁄ PAGE and stained by Coomassie brilliant blue An amount

equivalent to 2 lg of chlorophyll was loaded in each lane PsbO1,

PsbO2; 4 mol PsbO1 or PsbO2 per PSII, 1 : 1; 1 mole PsbO1 and

1mole PsbO2 per PSII, 2 : 2; 2 mole PsbO1 and 2 mole PsbO2 per

PSII (B) Relative oxygen-evolving activity of PSII reconstituted with

an equimolar mixture of PsbO1 and PsbO2 The maximum rate of

oxygen evolution (100%) equals the rate measured for untreated

PSII minus that for urea-washed PSII (C) Reconstitution of PSII

with PsbOs in which the ratio of PsbO1 to total PsbO was varied.

The relative oxygen-evolving activity (r) and the ratio of bound

PsbO1 : PsbOs (h) The maximum rate of oxygen evolution (100%)

equals the rate measured for untreated PSII minus that for

urea-washed PSII The ratio of bound PsbO1 : PsbOs was estimated

from the Coomassie brilliant blue-staining on SDS⁄ PAGE Standard

deviations were calculated from five measurements.

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However, the oxygen-evolving activity of

urea-washed PSII particles reconstituted with PsbO1-2-1

was similar to that of the particles reconstituted with

PsbO1 (Fig 5C) A lower level of activity was

observed with PsbO1-1-2, a chimera with the

C-ter-minal sequence of PsbO2 Although the difference was

small, the same results were obtained repeatedly These

results suggest that the difference in surface charge

between PsbO1 and PsbO2 did not affect the difference

in oxygen-evolving activity

C-Terminal amino acid substitution and

oxygen-evolving activity

PsbO1 and PsbO1-1-2 had three amino acid changes;

Val186 (PsbO1) to Ser (PsbO2), Val204 to Ile, and

Leu246 to Ile (Fig 6A) To examine which

replace-ment was responsible for the difference in the

oxygen-evolving activity, we prepared mutated PsbO1 in which

an amino acid was substituted for the corresponding

one in PsbO2 (V186S, V204I and L246I)

Measure-ment of the oxygen-evolving activity upon

reconstitu-tion with the spinach PSII core showed that the

activity levels with V186S and L246I were apparently

lower than that with PsbO1 (Fig 6B), suggesting that

these two amino acids were responsible for the lower

level of activity Unexpectedly, V204I showed stronger

oxygen-evolving activity than PsbO1

We next prepared double-mutated proteins with two

amino acid substitutions; i.e V186S⁄ V204I, V186S ⁄

L246I and V204I⁄ L246I The oxygen-evolving activity

reconstituted with V186S⁄ V204I and V204I ⁄ L246I was

similar to that with PsbO1; levels were higher than for

V186S and L246I and lower than for V204I (Fig 6B)

The activity reconstituted with V186S⁄ L246I was much

weaker than that with V186S, L246I or PsbO2 These

results confirmed that the replacement of Val186 with

Ser and Leu146 with Ile led to a reduction in the level

of oxygen-evolving activity, while the replacement of

Val204 with Ile led to an increase

Location of amino acids that differ between

PsbO1 and PsbO2

The locations of three amino acids, Val186 Val204 and

Leu246, were predicted using the Thermosynechococcus

elongatusPsbO [19] (protein data bank accession

num-ber; 1S5L) as a template The prediction suggested that

Val186, Val204 and Leu246 were dispersed in different

secondary structures; i.e in the a-helix, in the b-sheet

and near the b-sheet, respectively (Fig 7) The

predic-tion also supported the nopredic-tion that these replacements

independently affected the oxygen-evolving activity As

expected, the predicted structure of Arabidopsis PsbO2 was very similar to the structure of PsbO1 (data not shown), and the substitution of amino acids between PsbO1 and PsbO2 would not modify the overall struc-ture of PsbO

Discussion The existence of two psbO genes enabled the isolation

of psbo1 which lacked psbO1 expression and showed weak photosynthetic activity In this study, we exam-ined the functional role of two PsbOs in Arabidopsis Careful characterization of the PsbOs in psbo1 and the wild type (Fig 2A) showed that psbo1 showed a much greater accumulation of PsbO2 than in the wild type This finding suggests a compensational mechanism that stimulates the expression of PsbO2 when a functional psbO1 gene is absent The shortage of PsbOs caused a photosynthetic defect in psbo1, especially in young psbo1 However, mature psbo1 exhibited increased lev-els of PsbO and improved photosynthetic activity, as estimated from the increased Fv⁄ Fm, but the molecular mechanism of this adaptation to a genetic defect is not clear

Our immunoblot analysis also showed that the accumulation of PsbOs limited the levels of other PSII proteins as well as the efficiency of PSII This result was consistent with findings in early studies using higher-plant PSII that the extraction of PsbO from PSII affected the stability of PsbA and the assembly of other extrinsic proteins [22–24] In this respect, the quite different phenotypes observed in psbo1 and psbO-deletion mutants of green algae and cyanobacteria might lead to a clearer understanding

of the structure of the oxygen-evolving complex [6,7] First, although a psbO-deletion mutant of the Chlamydomonas reinhardtii [8] also had an enhanced turnover of core PSII polypeptide, PsbA, a psbO-deletion mutant of cyanobacteria accumulated PSII reaction centers at nearly normals levels The differ-ence in the behavior of the deletion mutants between higher plants, green algae and cyanobacteria suggests

a difference in the relationship between the extrinsic proteins Green algae and higher plants contain PsbP and PsbQ, whereas cyanobacteria contain PsbV and PsbU There is an apparent difference between PsbP and PsbV, as PsbP cannot bind to the PSII core or function in the absence of PsbO, but PsbV alone functions effectively in the absence of PsbO Second, PsbP was accumulated at normal levels in the Chlamydomonas reinhardtii psbO-deletion mutant, sug-gesting a difference between higher plants and green algae in the regulation of levels of extrinsic proteins

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Arabidopsis thaliana O1

Arabidopsis thaliana O2

Nicotiana tabacum

Solanum tuberosum

Lycopersicon esculentum

Pisum sativum

Oryza sativa

Spinacia oleracea

Volvox carteri

Chlamydomonas reinhardtii

Euglena gracilis

Bigelowiella natans

Synechocystis sp PCC 6803

Anabaena sp PCC 7120

Thermosynechococcus elongatus BP-1

Prochlorococcus marinus SS120

Prochlorococcus marinus MIT9313

Synechococcus sp.WH8102

Triticum aestivum

Fritillaria agrestis

*

Synechocystis sp PCC 6803

Prochlorococcus marinus SS120

Prochlorococcus marinus MIT9313

Synechococcus sp.WH8102

Arabidopsis thaliana O1

Arabidopsis thaliana O2

Nicotiana tabacum

Solanum tuberosum

Lycopersicon esculentum

Pisum sativum

Oryza sativa

Spinacia oleracea

Volvox carteri

Chlamydomonas reinhardtii

Euglena gracilis

Bigelowiella natans

Anabaena sp PCC 7120

Thermosynechococcus elongatus BP-1

Triticum aestivum

Fritillaria agrestis

*

Arabidopsis thaliana O1

Arabidopsis thaliana O2

Nicotiana tabacum

Solanum tuberosum

Lycopersicon esculentum

Pisum sativum

Oryza sativa

Spinacia oleracea

Volvox carteri

Chlamydomonas reinhardtii

Euglena gracilis

Bigelowiella natans

Synechocystis sp PCC 6803

Anabaena sp PCC 7120

Thermosynechococcus elongatus BP-1

Prochlorococcus marinus SS120

Prochlorococcus marinus MIT9313

Synechococcus sp.WH8102

Triticum aestivum

Fritillaria agrestis

*

Relative oxygen-evolving activity

0 20 40 60 80 100 120 PsbO1

PsbO2 V186S V204I L246I 186&204 186&246 204&246

Fig 6 Determination of the amino acid changes responsible for the alteration of protein function (A) Alignments around the replacements between PsbO1 and PsbO1-1-2 The alignments were made with CLUSTAL W Asterisks indicate substituted residues with Arabidopsis PsbO1 and PsbO2 Arabidopsis PsbO1 and PsbO2 are underlined (B) Oxygen-evolving activities reconstituted with PsbO1, PsbO2, and mutated-PsbOs The maximum rate of oxygen evolution (100%) equals the rate measured for untreated PSII minus that for urea-washed PSII Stand-ard deviations were calculated from five measurements.

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Interestingly, PsbO1 and PsbO2 showed different

biochemical activity at reconstituting oxygen-evolving

activity with urea-washed PSII isolated from spinach;

the restoration of oxygen-evolving activity with PsbO2

was about 80% of that with PsbO1, whereas the

bind-ing affinities of PsbO1 and PsbO2 were similar A

recent study on the structure of PSII [19] suggested

that PSII has one copy of PsbO, but early works

[16,25] and our study (Fig 3) showed that the

maximum oxygen-evolving activity reconstituted with

both PsbO was achieved at about two PsbOs per PSII

It is not clear why about two PsbOs per PSII are nee-ded for the maximum activity

The chimeric PsbO derived from PsbO1 and PsbO2 clearly indicated that the surface charge was not crit-ical for the different activities of PsbO1 and PsbO2, whereas negative and positive charges of amino acids have been reported to be important for the interaction between PsbO and PSII [5,17,18] The analysis using the chimeric PsbOs showed that three amino acid replacements at the C-terminus affected the restoration

of oxygen-evolving activity

As predicted in Fig 7, the three amino acids were dispersed in PsbO Interestingly, although Val186 was not conserved in higher plants, green algae and cyano-bacteria, its substitution with Ser decreased oxygen-evolving activities On the other hand, when Val204 of PsbO1, which is conserved in higher plants except for Arabidopsis PsbO2, was substituted with the Ile of PsbO2, this mutated-protein restored the oxygen-evol-ving activity better than PsbO1 It should be noted that the amino acid at this position is substituted with Ile in both green algae and cyanobacteria By contrast, Leu246 is conserved in all higher plants and green algae, except in PsbO2 PsbO2 has Ile246, which is substituted with Ile or Val in cyanobacteria, except for Prochlorococcus marinus which has Lys The replace-ment of Leu with Ile was shown to result in a reduc-tion of the restorareduc-tion of oxygen-evolving activity It has been reported that Leu at position 246 was critical for PsbO to bind PSII and the restoration of oxygen-evolving activity in spinach [29] Although our recon-stitution experiment with PsbO2 showed a similar affinity for PSII particles as PsbO1, the importance of this amino acid residue for oxygen-evolving activity was consistent with the results of previous works [29,30] The similar chemical properties of Leu and Ile might explain their similar binding affinities It has also been reported that the C-terminal peptide of PsbO (15 amino acids) competed with mature PsbO to bind the PSII core, suggesting that the C-terminus of PsbO plays an important role in the interaction with an integral part of the PSII core [31] Identification of the importance of the three amino acid residues in PsbO, especially V204I, could be useful for understanding the efficiency of PSII

In vivo and in vitro experiments have shown that both a shortage of the PsbOs and a lower level of oxy-gen-evolving activity resulted in the poor photosyn-thetic activity and retarded growth in psbo1 In most higher plants, such as spinach, pea and rice, PsbO is encoded by only a single gene [26,32] The existence of

a duplicated psbO gene in Arabidopsis should help us to understand the molecular selection of duplicated genes

L246I

V186S

V186S

V204I

L246I

A

B

Fig 7 The location of three amino acid substitutions between

PsbO1 and PsbO2 (A) Stereoview of Thermosynechococcus

elong-atus PsbO The corresponding positions of Val186, Val204 and

Leu246 in Thermosynechococcus elongatus PsbO were predicted

by SwissModel (http://swissmodel.expasy.org//SWISS-MODEL.

html) and are shown in red and indicated by an arrow (B)

Stereo-view of PsbO, PsbA and Mn clusters in Thermosynechococcus

elongatus PsbO: green, PsbA: blue, Mn clusters: pink, The

posi-tions corresponding to Val-186, Val-204 and Leu-246 are shown in

red and indicated by an arrow These figures were generated with

P Y MOL (http://pymol.sourceforge.net/).

Trang 9

In Arabidopsis, psbQ was also encoded by two

nuc-lear genes (At4g21280 and At4g05180) with about

82% similarity at the gene level On the other hand,

psbP (At1g06680) has a similar but nonfunctional gene

(At2g30790) (about 84% similarity at the gene level); it

encodes a much smaller protein than PsbP, suggesting

that the isogene of psbP recently lost its function

Simi-larly, other subunits in PSII encoded by nuclear genes,

such as psbR and psbS, are encoded by a single gene

The investigation of PsbQ isogenes should provide

another clue as to the physiological role of duplicated

genes for extrinsic proteins in the oxidation of water

Although the duplicated genes would initially have

had the same functions, the accumulation of mutations

over time has resulted in either the functional loss of one

copy or functional divergence between them (our data

and [33]) It is not clear how much functional

differenti-ation exists between PsbO1 and PsbO2 and whether the

inferior psbO2 will lose its activity At present, the

data-base (Brassica Genome Gateway, http://brassica.bbsrc

ac.uk) suggests that Brassica rapa and Brassica napus

have a psbO1-like gene (accession number; Brassica

rapa, BQ791144 and Brassica napus, AF139818) and a

psbO2-like gene (accession number; Brassica rapa,

BG543314 and Brassica napus, CD821869), indicating

that any potential evolutionary pressure to remove the

psbO2 gene is not strong Indeed, PsbO2 might have

some physiological significance; for example, the poor

oxygen-evolving activity with PsbO2 might be

advanta-geous under excessive light conditions

Conclusions

The psbO2 gene could not complement the defect in

the psbO1 gene for both quantitative and qualitative

reasons: a shortage of PsbOs and the poor

oxygen-evolving activity of PsbO2 The functional difference

between PsbO1 and PsbO2 in the restoration of

oxygen-evolving activity was ascribed to three amino

acid replacements at the C-terminus; Val186 in PsbO1

for Ser in PsbO2, Val204 for Ile, and Leu246 for Ile

Experimental procedures

Plant growth and measurements of chlorophyll

fluorescence

Seeds of the wild-type and psbo1 were sown in soil after

Lehle Seeds (Round Rock, TX, USA) They were grown at

with a 9-h light (from 09:00–18:00 h): 15-h dark cycle for

2 months

fluorometer (Waltz, Effeltrich, Germany) The minimum

fluores-cence at closed PSII centers in the dark) was measured by applying a 1-s pulse of saturating white light

Immunoblot analysis Thylakoid membranes were isolated from wild-type and

[34] Protein samples were prepared in sample buffer

5% glycerol, and 5% 2-mercaptoethanol], and analyzed by

expression with Coomassie brilliant blue staining [35] Thyl-akoid membranes were loaded on a chlorophyll basis The protein analysis with respect to the protein content showed the results similar to that on a chlorophyll basis The thy-lakoid proteins were also transferred to a polyvinylidene difluoride membrane with a semidry blotting system [36], and detected with rabbit antiserum against spinach PsbO, kindly provided by the late A Watanabe of the University

of Tokyo, or rabbit antiserum against spinach D1 protein (PsbA), provided by Y Yamamoto (Division of Integrated Life Science, Kyoto University, Japan) The chlorophyll concentration was measured by spectrophotometry in 80% acetone [37]

The amounts of PsbO, PsbA and PsbP in plants were quantified from immunoblots and bound PsbOs to urea-washed PSII were quantified from Coomassie brilliant blue-stained plates Image analysis was performed using the public-domain software nih-image (version 1.62)

Preparation of recombinant PsbOs The recombinant PsbO1 and PsbO2 were expressed and purified as described previously [38] The expression vectors for the chimeric proteins were produced by digestion of psbO1- and psbO2-pET 21d + with BamHI, NotI or PpuMI and by the ligation of resultant fragments Site-directed mutagenesis was performed according to the proto-col for the Quick-change Site-directed Mutagenesis Kit (Stratagene) and a Technical Review for Long polymerase-chain reaction using KOD plus (TOYOBO, Osaka, Japan) All mutant constructs were confirmed by DNA sequencing These mutant proteins were purified similar to the original PsbO1 and PsbO2

Reconstitution of PSII with recombinant PsbOs Photosystem II membranes were isolated from spinach leaves purchased at a local market according to the method

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of Ghanotakis et al [39] Native extrinsic proteins in PSII

were extracted by incubation in urea-washed buffer (50 mm

Mes–NaOH (pH 8.3) and 3 m urea), to give urea-washed

PSII particles Recombinant PsbOs were mixed with

urea-washed PSII particles and incubated at room temperature

concentration of PSII was estimated on the basis of chl

concentrations and a stoichiometry of 250 chlorophylls per

PSII complex

(Hansatech, UK) in the presence of 2 mm DCBQ

(dichloro-p-quinone) as the electron acceptor for PSII Red

in conjunction with an HA50 heat-absorbing filter and an

R-60 red optical filter (Kenko, Tokyo, Japan)

Alignment of PsbOs

Similarity was evaluated using the clustal w program

[40–42] The alignment parameters used were: protein mass

matrix: BLOSUM series, gap opening penalty (GOP): 10.0,

gap extension penalty (GEP): 0.05 and Delay divergent

sequences: 40%

Acknowledgements

This study was supported in part by a COE Scientific

Research Grant from the Ministry of Education,

Cul-ture, Sports, Science and Technology of Japan

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