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Query: UMLS:C1832526 (PCC)
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Photosystem II (PSII) is prone to irreversible light-induced damage, with the D1 polypeptide a major target. Repair processes operate in the cell to replace a damaged D1 subunit within the complex with a newly synthesized copy. As yet, the molecular details of PSII repair are relatively obscure despite the critical importance of this process for maintaining PSII activity and cell viability. We are using the cyanobacterium Synechocystis sp. PCC 6803 to identify the various proteases and chaperones involved in D1 turnover in vivo. Two families of proteases are being studied: the FtsH family (four members) of Zn(2+)-activated nucleotide-dependent proteases; and the HtrA (or DegP) family (three members) of serine-type proteases. In this paper, we report the results of our studies on a triple mutant in which all three copies of the htrA gene family have been inactivated. Growth of the mutant on agar plates was inhibited at high light intensities, especially in the presence of glucose. Oxygen evolution measurements indicated that, under conditions of high light, the rate of synthesis of functional PSII was less in the mutant than in the wild-type. Immunoblotting experiments conducted on cells blocked in protein synthesis further indicated that degradation of D1 was slowed in the mutant. Overall, our observations indicate that the HtrA family of proteases are involved in the resistance of Synechocystis 6803 to light stress and play a part, either directly or indirectly, in the repair of PSII in vivo.
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PMID:Involvement of the HtrA family of proteases in the protection of the cyanobacterium Synechocystis PCC 6803 from light stress and in the repair of photosystem II. 1243 85

With respect to the mechanism of chaperone-like activity, we examined the behavior of haptoglobin under heat shock conditions. Secondary structure changes during heat treatment were followed by circular dichroism, Raman and infrared spectroscopy. A model of the haptoglobin tetramer, based on its sequence homology with serine proteases and the CCP modules, has been proposed. Sequence regions responsible for the chaperone-like activity were not fully identical with the region that takes part in formation of the hemoglobin-haptoglobin complex. We can postulate the presence of at least two different chaperone-binding sites on each haptoglobin heavy chain.
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PMID:Study of chaperone-like activity of human haptoglobin: conformational changes under heat shock conditions and localization of interaction sites. 1245 43

Photosystem I (PS I) is a transmembranal multisubunit complex that mediates light-induced electron transfer from plactocyanine to ferredoxin. The electron transfer proceeds from an excited chlorophyll a dimer (P700) through a chlorophyll a (A0), a phylloquinone (A1), and a [4Fe-4S] iron-sulfur cluster FX, all located on the core subunits PsaA and PsaB, to iron-sulfur clusters FA and FB, located on subunit PsaC. Earlier, it was attempted to determine the function of FX in the absence of FA/B mainly by chemical dissociation of subunit PsaC. However, not all PsaC subunits could be removed from the PS I preparations by this procedure without partially damaging FX. We therefore removed subunit PsaC by interruption of the psaC2 gene of PS I in the cyanobacterium Synechocystis sp. PCC 6803. Cells could not grow under photosynthetic conditions when subunit PsaC was deleted, yet the PsaC-deficient mutant cells grew under heterotrophic conditions and assembled the core subunits of PS I in which light-induced electron transfer from P700 to A1 occurred. The photoreduction of FX was largely inhibited, as seen from direct measurement of the extent of electron transfer from A1 to FX. From the crystal structure it can be seen that the removal of subunits PsaC, PsaD, and PsaE in the PsaC-deficient mutant resulted in the braking of salt bridges between these subunits and PsaB and PsaA and the formation of a net of two negative surface charges on PsaA/B. The potential induced on FX by these surface charges is proposed to inhibit electron transport from the quinone. In the complete PS I complex, replacement of a cysteine ligand of FX by serine in site-directed mutation C565S/D566E in subunit PsaB caused an approximately 10-fold slow down of electron transfer from the quinone to FX without much affecting the extent of this electron transfer compared with wild type. Based on these and other results, we propose that FX might have a major role in controlling electron transfer through PS I.
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PMID:Control of electron transport in photosystem I by the iron-sulfur cluster FX in response to intra- and intersubunit interactions. 1262 5

Early diagnosis of rheumatoid arthritis (RA) is important since aggressive therapy should begin at an early stage. Diagnosis is made on a clinical basis, supported by the determination of rheumatoid factor (RF). However, RF is also positive in healthy subjects, as well as in other autoimmune and infectious diseases. Two other diagnostic markers with a high specificity for RA, antiperinuclear factor (APF) and antikeratin antibodies (AKA), are not in general use because of technical difficulties. APF and AKA are antifilaggrin antibodies (AFA) that bind to determinants rich in the unusual amino acid citrulline, generated by posttranscriptional modification of arginine residues by the enzyme peptidylarginine deiminase (PAD). Enzymatic determination of recombinant filaggrin fragments produces linear peptides, which are recognized by RA-specific autoantibodies. After substitution of serine by cysteine, a cyclic peptide is formed. The conformational change mimics the original structure of the filaggrin and enhances the affinity of the antibodies. Recently, an anti-cyclic citrullinated peptide (anti-CCP) ELISA was developed. The sensitivity of this test is usually 51%-68%, with a specificity of about 96%-98% (significantly higher than that of RF). Together with RF, anti-CCP increases the ability to diagnose patients with early RA. The test might help to predict which patients will develop persistent disease with evidence of radiologic lesions. Implementation of the highly specific anti-CCP test in conjunction with RF would enable reliable early diagnosis in some cases and allow the initiation of aggressive therapy with disease modifying anti-rheumatic drugs (DMARDs).
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PMID:[Anti-cyclic citrullinated peptide antibodies as a diagnostic test for rheumatoid arthritis]. 1269 70

P(II) proteins signal the cellular nitrogen status in numerous bacteria, and in cyanobacteria P(II) is subjected to serine phosphorylation when the cells experience a high C to N balance. In the unicellular cyanobacterium Synechococcus sp. PCC 7942, the P(II) protein (glnB gene product) is known to mediate the ammonium-dependent inhibition of nitrate and nitrite uptake. The analysis of gene expression through RNA/DNA hybridization indicated that a P(II)-null mutant was also impaired in the induction of NtcA-dependent, nitrogen assimilation genes amt1 (ammonium permease), glnA (glutamine synthetase) and nir (nitrite reductase), as well as of the N-control gene ntcA, mainly under nitrogen deprivation. This gene expression phenotype of the glnB mutant could be complemented by wild-type P(II) protein or by modified P(II) proteins that cannot be phosphorylated and mimic either the phosphorylated (GlnB(S49D) and GlnB(S49E)) or unphosphorylated (GlnB(S49A)) form of P(II). However, strains carrying the GlnB(S49D) and GlnB(S49E) mutant proteins exhibited higher levels of expression of nitrogen-regulated genes than the strains carrying the wild-type P(II) or the GlnB(S49A) protein.
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PMID:Transcriptional effects of the signal transduction protein P(II) (glnB gene product) on NtcA-dependent genes in Synechococcus sp. PCC 7942. 1275 2

In previous work, some members of our group isolated mutant strains of Synechocystis sp. strain PCC 6803 in which point mutations had been inserted into the psaC gene to alter the cysteine residues to the F(A) and F(B) iron-sulfur clusters in the PsaC subunit of photosystem I (J. P. Yu, I. R. Vassiliev, Y. S. Jung, J. H. Golbeck, and L. McIntosh, J. Biol. Chem. 272:8032-8039, 1997). These mutant strains did not grow photoautotrophically due to suppressed levels of chlorophyll a and photosystem I. In the results described here, we show that suppressor mutations produced strains that are capable of photoautotrophic growth at moderate light intensity (20 micromol m(-2) s(-1)). Two separate suppressor strains of C14S(PsaC), termed C14S(PsaC)-R62 and C14S(PsaC)-R18, were studied and found to have mutations in a previously uncharacterized open reading frame of the Synechocystis sp. strain PCC 6803 genome named sll0088. C14S(PsaC)-R62 was found to substitute Pro for Arg at residue 161 as the result of a G482-->C change in sll0088, and C14S(PsaC)-R18 was found to have a three-amino-acid insertion of Gly-Tyr-Phe following Cys231 as the result of a TGGTTATTT duplication at T690 in sll0088. These suppressor strains showed near-wild-type levels of chlorophyll a and photosystem I, yet the serine oxygen ligand to F(B) was retained as shown by the retention of the S > or = 3/2 spin state of the [4Fe-4S] cluster. The inactivation of sll0088 by insertion of a kanamycin resistance cartridge in the primary C14S(PsaC) mutant produced an engineered suppressor strain capable of photoautotrophic growth. There was no difference in psaC gene expression or in the amount of PsaC protein assembled in thylakoids between the wild type and an sll0088 deletion mutant. The sll0088 gene encodes a protein predicted to be a transcriptional regulator with sequence similarities to transcription factors in other prokaryotic and eukaryotic organisms, including Arabidopsis thaliana. The protein contains a typical helix-turn-helix DNA-binding motif and can be classified as a negative regulator by phylogenetic analysis. This suggests that the product of sll0088 has a role in regulating the biogenesis of photosystem I.
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PMID:Suppressor mutations in the study of photosystem I biogenesis: sll0088 is a previously unidentified gene involved in reaction center accumulation in Synechocystis sp. strain PCC 6803. 1281 82

IscA homologues are involved in iron-sulfur cluster biosynthesis. In the non-nitrogen-fixing cyanobacterium Synechocystis PCC 6803, there are two IscA homologues, SLR1417 and SLR1565 (designated IscA1 and IscA2), of which only IscA2 exists as a protein complex with the HEAT-repeat-containing protein, SLR1098 (IaiH). We observed that the absorption spectrum of the recombinant IscA2/IaiH complex resembles that of IscA2 alone, although it is sharper. In the presence of dithiothreitol, the [2Fe-2S] cluster of IscA2 alone, but not of the IscA2/IaiH complex, became reductively labile upon the addition of sodium dithionite. This implies that the IscA2 moiety of the [2Fe-2S] cluster is stabilized by the presence of IaiH. The [2Fe-2S] cluster of the IscA2/IaiH complex was destabilized by sodium dithionite in the absence of dithiothreitol, suggesting that the in vivo stability of the iron-sulfur cluster in the IscA2/IaiH complex is influenced by the redox state of cellular thiols. When any one of three conserved cysteine residues in IscA2, potential ligands for the [2Fe-2S] cluster, was replaced with serine, the amount of assembled [2Fe-2S] cluster and protein complex was significantly reduced in E. coli cells. The cysteine mutated IscA2/IaiH complexes that were present all contained a [2Fe-2S]-like cluster suggesting that the assembly of a stable iron-sulfur cluster bound to IscA2 is required for efficient and stable complex formation. Truncated IaiH proteins were analyzed using the yeast two-hybrid assay to identify the essential domain of IaiH that interacts physically with IscA2. At least 2 of the 5 N-terminal HEAT repeats of IaiH were found to be required for interaction with IscA2.
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PMID:A HEAT-repeats containing protein, IaiH, stabilizes the iron-sulfur cluster bound to the cyanobacterial IscA homologue, IscA2. 1296 69

Light-dependent regulation of a growing number of chloroplast enzymatic activities has been found to occur through the reversible reduction of intra- or intermolecular disulphides by thioredoxins. In cyanobacteria, despite their similarity to chloroplasts, no proteins have hitherto been shown to interact with thioredoxins, and the role of the cyanobacterial ferredoxin/thioredoxin system has remained obscure. By using an immobilized cysteine 35-to-serine site-directed mutant of the Synechocystis sp. PCC 6803 thioredoxin TrxA as bait, we screened the Synechocystis cytosolic and peripheral membrane protein complements for proteins interacting with TrxA. The covalent bond between the isolated target proteins and mutated TrxA was confirmed by nonreducing/reducing two-dimensional SDS/PAGE. Thus, we have identified 18 cytosolic proteins and 8 membrane-associated proteins as candidate thioredoxin substrates. Twenty of these proteins have not previously been associated with thioredoxin-mediated regulation. Phosphoglucomutase, one of the previously uncharacterized thioredoxin-linked enzymes, has not earlier been considered a target for metabolic control through disulphide reduction. In this article, we show that phosphoglucomutase is inhibited under oxidizing conditions and activated by DTT and reduced wild-type TrxA in vitro. The results imply that thioredoxin-mediated redox regulation is as extensive in cyanobacteria as in chloroplasts but that the subjects of regulation are largely different.
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PMID:Thioredoxin-linked processes in cyanobacteria are as numerous as in chloroplasts, but targets are different. 1467 18

This communication presents a short outline of the current knowledge on the molecular basis of P(II) signal transduction in unicellular cyanobacteria with respect to the perception of environmental stimuli. First, the general characteristics of the P(II) signalling system in unicellular cyanobacteria are presented, the hallmark of which is modification by serine-phosphorylation, as compared to the paradigmatic P(II) signal transduction system in proteobacteria, which is based on tyrosyl-uridylylation. Then, the focus is turned on the signals controlling P(II) phosphorylation state. Recently, the cellular phosphatase (termed PphA), which specifically dephosphorylates phosphorylated P(II) (P(II)-P) was identified in Synechocystis sp. strain PCC 6803. With the availability of a PphA-deficient mutant and the purified components for in vitro assay of PphA mediated P(II)-P dephosphorylation, novel insights into the signals, to which P(II)-P dephosphorylation responds, can be obtained. Here we present an investigation of the response of P(II)-P dephosphorylation towards treatments that affect the redox-balance of the cells. Furthermore, a possible role of varying ATP/ADP ratios on P(II)-P dephosphorylation was examined. From these studies, together with previous investigations, we conclude that P(II)-P dephosphorylation specifically responds to changes in the levels of central metabolites of carbon metabolism, in particular 2-oxoglutarate.
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PMID:P signalling in unicellular cyanobacteria: analysis of redox-signals and energy charge. 1503 76

A family of serine proteases mediates the proteolytic cascades of several defense mechanisms in vertebrates, such as the complement system, blood coagulation and fibrinolysis. These proteases usually form large complexes with other glycoproteins. Their common features are their modular structures and restricted substrate specificities. The lectin pathway of complement, where mannose-binding lectin (MBL) recognizes the carbohydrate structures on pathogens, is activated by mannose-binding lectin-associated serine protease-2 (MASP-2). We present the 2.25A resolution structure of the catalytic fragment of MASP-2 encompassing the second complement control protein module (CCP2) and the serine protease (SP) domain. The CCP2 module stabilizes the structure of the SP domain as demonstrated by differential scanning calorimetry measurements. The asymmetric unit contains two molecules with different CCP-SP domain orientations, reflecting increased modular flexibility at the CCP2/SP joint. This flexibility may partly explain the ability of the MASP-2 dimer to perform all of its functions alone, whereas the same functions are mediated by the much larger C1r2-C1s2 tetramer in the C1 complex of the classical pathway. The main scaffold of the MASP-2 SP domain is chymotrypsin-like. Eight surface loops determine the S1 and other subsite specificities. Surprisingly, some surface loops of MASP-2, e.g. loop 1 and loop 2, which form the S1 pocket are similar to those of trypsin, and show significant differences if compared with those of C1s, indicating that the nearly identical substrate specificities of C1s and MASP-2 are realized through different sets of enzyme-substrate interactions.
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PMID:The structure of MBL-associated serine protease-2 reveals that identical substrate specificities of C1s and MASP-2 are realized through different sets of enzyme-substrate interactions. 1536 79


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