RSRA_STRCO
ID RSRA_STRCO Reviewed; 105 AA.
AC Q7AKG8; Q9RL96;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2012, sequence version 1.
DT 03-AUG-2022, entry version 51.
DE RecName: Full=Anti-sigma factor RsrA;
DE AltName: Full=Regulator of SigR;
DE AltName: Full=Sigma-R anti-sigma factor RsrA;
GN Name=rsrA; OrderedLocusNames=SCO5217;
OS Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces; Streptomyces albidoflavus group.
OX NCBI_TaxID=100226;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION AS AN ANTI-SIGMA FACTOR,
RP INTERACTION WITH SIGR, SUBUNIT, AND POSSIBLE DISULFIDE BONDS.
RC STRAIN=ATCC BAA-471 / A3(2) / M145;
RX PubMed=10428967; DOI=10.1093/emboj/18.15.4292;
RA Kang J.G., Paget M.S.B., Seok Y.J., Hahn M.Y., Bae J.B., Hahn J.S.;
RT "RsrA, an anti-sigma factor regulated by redox change.";
RL EMBO J. 18:4292-4298(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-471 / A3(2) / M145;
RX PubMed=12000953; DOI=10.1038/417141a;
RA Bentley S.D., Chater K.F., Cerdeno-Tarraga A.-M., Challis G.L.,
RA Thomson N.R., James K.D., Harris D.E., Quail M.A., Kieser H., Harper D.,
RA Bateman A., Brown S., Chandra G., Chen C.W., Collins M., Cronin A.,
RA Fraser A., Goble A., Hidalgo J., Hornsby T., Howarth S., Huang C.-H.,
RA Kieser T., Larke L., Murphy L.D., Oliver K., O'Neil S., Rabbinowitsch E.,
RA Rajandream M.A., Rutherford K.M., Rutter S., Seeger K., Saunders D.,
RA Sharp S., Squares R., Squares S., Taylor K., Warren T., Wietzorrek A.,
RA Woodward J.R., Barrell B.G., Parkhill J., Hopwood D.A.;
RT "Complete genome sequence of the model actinomycete Streptomyces coelicolor
RT A3(2).";
RL Nature 417:141-147(2002).
RN [3]
RP FUNCTION AS A DISULFIDE STRESS SENSOR, COFACTOR, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF CYS-3; CYS-11; CYS-31; CYS-41; CYS-44; CYS-61 AND CYS-62.
RC STRAIN=ATCC BAA-471 / A3(2) / M145;
RX PubMed=11251822; DOI=10.1046/j.1365-2958.2001.02298.x;
RA Paget M.S., Bae J.B., Hahn M.Y., Li W., Kleanthous C., Roe J.H.,
RA Buttner M.J.;
RT "Mutational analysis of RsrA, a zinc-binding anti-sigma factor with a
RT thiol-disulphide redox switch.";
RL Mol. Microbiol. 39:1036-1047(2001).
RN [4]
RP FUNCTION AS AN ANTI-SIGMA FACTOR, AND INTERACTION WITH SIGR.
RC STRAIN=ATCC BAA-471 / A3(2) / M145;
RX PubMed=12381317; DOI=10.1016/s0022-2836(02)00948-8;
RA Li W., Stevenson C.E., Burton N., Jakimowicz P., Paget M.S., Buttner M.J.,
RA Lawson D.M., Kleanthous C.;
RT "Identification and structure of the anti-sigma factor-binding domain of
RT the disulphide-stress regulated sigma factor sigma(R) from Streptomyces
RT coelicolor.";
RL J. Mol. Biol. 323:225-236(2002).
RN [5]
RP FUNCTION AS AN ANTI-SIGMA FACTOR, INTERACTION WITH SIGR, COFACTOR,
RP DISULFIDE BOND, AND MASS SPECTROMETRY.
RC STRAIN=ATCC BAA-471 / A3(2) / M145;
RX PubMed=14529630; DOI=10.1016/j.jmb.2003.08.038;
RA Li W., Bottrill A.R., Bibb M.J., Buttner M.J., Paget M.S., Kleanthous C.;
RT "The role of zinc in the disulphide stress-regulated anti-sigma factor RsrA
RT from Streptomyces coelicolor.";
RL J. Mol. Biol. 333:461-472(2003).
RN [6]
RP ZINC-BINDING, AND MUTAGENESIS OF HIS-37.
RC STRAIN=ATCC BAA-471 / A3(2) / M145;
RX PubMed=16819828; DOI=10.1021/bi060711v;
RA Zdanowski K., Doughty P., Jakimowicz P., O'Hara L., Buttner M.J.,
RA Paget M.S., Kleanthous C.;
RT "Assignment of the zinc ligands in RsrA, a redox-sensing ZAS protein from
RT Streptomyces coelicolor.";
RL Biochemistry 45:8294-8300(2006).
RN [7]
RP FUNCTION, AND REDUCTION BY MYCOTHIOL.
RC STRAIN=ATCC BAA-471 / A3(2) / M145;
RX PubMed=18430082; DOI=10.1111/j.1365-2958.2008.06191.x;
RA Park J.H., Roe J.H.;
RT "Mycothiol regulates and is regulated by a thiol-specific antisigma factor
RT RsrA and sigma(R) in Streptomyces coelicolor.";
RL Mol. Microbiol. 68:861-870(2008).
RN [8]
RP MUTAGENESIS OF 33-LYS--LYS-47; HIS-37; PHE-38; GLU-39; GLU-40; CYS-41;
RP PRO-43; CYS-44; LEU-45 AND GLU-46.
RC STRAIN=ATCC BAA-471 / A3(2) / M145;
RX PubMed=21685450; DOI=10.1093/nar/gkr477;
RA Jung Y.G., Cho Y.B., Kim M.S., Yoo J.S., Hong S.H., Roe J.H.;
RT "Determinants of redox sensitivity in RsrA, a zinc-containing anti-sigma
RT factor for regulating thiol oxidative stress response.";
RL Nucleic Acids Res. 39:7586-7597(2011).
CC -!- FUNCTION: A redox-regulated anti-sigma factor for extracytoplasmic
CC function (ECF) sigma factor SigR, and a key sensor of disulfide stress.
CC Holds SigR, its cognate ECF sigma factor, in an inactive form,
CC inhibiting its sigma activity under reducing but not oxidizing
CC conditions; oxidation and reduction of the anti-sigma factor is
CC reversible. Mycothiol (MSH) is competent for reduction of RsrA,
CC allowing it to bind to SigR. In conjunction with its cognate sigma
CC factor SigR may sense the intracellular level of reduced MSH. Probably
CC releases SigR during oxidative stress. {ECO:0000269|PubMed:10428967,
CC ECO:0000269|PubMed:11251822, ECO:0000269|PubMed:12381317,
CC ECO:0000269|PubMed:14529630, ECO:0000269|PubMed:18430082}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:11251822, ECO:0000269|PubMed:14529630};
CC Note=Binds 1 Zn(2+) per subunit. Zinc is not required for SigR-binding,
CC but is required for anti-sigma factor activity. Zinc-binding renders
CC RsrA relatively resistant to oxidation. {ECO:0000269|PubMed:11251822,
CC ECO:0000269|PubMed:14529630};
CC -!- SUBUNIT: Interacts with cognate sigma factor SigR under reducing but
CC not oxiding conditions. Treatment with the thiol-oxidzing agent diamide
CC inhibits the interaction, while incubation with thioredoxin (trxA)
CC stimulates the interaction. {ECO:0000269|PubMed:10428967,
CC ECO:0000269|PubMed:12381317, ECO:0000269|PubMed:14529630}.
CC -!- PTM: Under oxidizing conditions up to 3 disulfide bonds are formed. A
CC single disulfide bond inhibits binding to SigR. Cys-11 forms a
CC disulfide bond with either Cys-44 (the major bind) or Cys-41 (a minor
CC bond).
CC -!- MASS SPECTROMETRY: Mass=12247; Method=SELDI; Note=Partially alkylated
CC with iodoacetamide, has 1 disulfide bond.;
CC Evidence={ECO:0000269|PubMed:14529630};
CC -!- MASS SPECTROMETRY: Mass=12361; Method=SELDI; Note=Full alkylated with
CC iodoacetamide.; Evidence={ECO:0000269|PubMed:14529630};
CC -!- DISRUPTION PHENOTYPE: Viable, but defective in sporulation, white
CC color. Strong induction of disulfide reductase (trxB) and thioredoxin-2
CC (trxC) that is not further induced by diamide. Acts as a SigR
CC constitutive mutant. A double sigR-rsrA mutant sporulates normally but
CC is more sensitive to diamide. {ECO:0000269|PubMed:11251822}.
CC -!- MISCELLANEOUS: A quadruple Cys-3-Ser, Cys-31-Ser, Cys-61-Ala, Cys-62-
CC Ala mutant has anti-sigma factor activity and is induced by diamide.
CC -!- SIMILARITY: Belongs to the zinc-associated anti-sigma factor (ZAS)
CC superfamily. {ECO:0000305}.
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DR EMBL; AJ010320; CAB61633.1; -; Genomic_DNA.
DR EMBL; AL939122; CAB94602.1; -; Genomic_DNA.
DR RefSeq; NP_629364.1; NC_003888.3.
DR RefSeq; WP_003973755.1; NZ_VNID01000008.1.
DR PDB; 5FRF; NMR; -; A=1-105.
DR PDB; 5FRH; NMR; -; A=1-105.
DR PDBsum; 5FRF; -.
DR PDBsum; 5FRH; -.
DR AlphaFoldDB; Q7AKG8; -.
DR SMR; Q7AKG8; -.
DR STRING; 100226.SCO5217; -.
DR GeneID; 1100658; -.
DR KEGG; sco:SCO5217; -.
DR PATRIC; fig|100226.15.peg.5301; -.
DR eggNOG; COG5662; Bacteria.
DR HOGENOM; CLU_155928_0_0_11; -.
DR InParanoid; Q7AKG8; -.
DR OMA; MSCGEPH; -.
DR PhylomeDB; Q7AKG8; -.
DR Proteomes; UP000001973; Chromosome.
DR GO; GO:0016989; F:sigma factor antagonist activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IMP:UniProtKB.
DR GO; GO:0051776; P:detection of redox state; IMP:UniProtKB.
DR GO; GO:0051775; P:response to redox state; IDA:UniProtKB.
DR GO; GO:0043934; P:sporulation; IMP:UniProtKB.
DR GO; GO:0030435; P:sporulation resulting in formation of a cellular spore; IEA:UniProtKB-KW.
DR InterPro; IPR024020; Anit_sigma_mycothiol_RsrA.
DR InterPro; IPR014295; Anti-sigma.
DR InterPro; IPR027383; Znf_put.
DR Pfam; PF13490; zf-HC2; 1.
DR TIGRFAMs; TIGR02949; anti_SigH_actin; 1.
DR TIGRFAMs; TIGR03988; antisig_RsrA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Metal-binding; Redox-active center;
KW Reference proteome; Sporulation; Transcription; Transcription regulation;
KW Zinc.
FT CHAIN 1..105
FT /note="Anti-sigma factor RsrA"
FT /id="PRO_0000423652"
FT REGION 33..47
FT /note="Contributes to redox-sensitivity"
FT REGION 86..105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 11
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 37
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305"
FT BINDING 41
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 44
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT DISULFID 11..44
FT /note="Or C-11 with C-41 (about 25%)"
FT /evidence="ECO:0000269|PubMed:14529630"
FT MUTAGEN 3
FT /note="C->S: No effect on sporulation, normal induction of
FT trxCp1."
FT /evidence="ECO:0000269|PubMed:11251822"
FT MUTAGEN 11
FT /note="C->S: No sporulation, constitutive expression of
FT trxCp1, no binding of SigR."
FT /evidence="ECO:0000269|PubMed:11251822"
FT MUTAGEN 31
FT /note="C->S: No effect on sporulation, normal induction of
FT trxCp1."
FT /evidence="ECO:0000269|PubMed:11251822"
FT MUTAGEN 33..47
FT /note="KFEHHFEECSPCLEK->VLNEHLETCEKCRKH: Inhibits SigR, no
FT diamide induction. A swap mutant with RsiW of B.subtilis."
FT /evidence="ECO:0000269|PubMed:21685450"
FT MUTAGEN 37
FT /note="H->A: No sporulation, constitutive disulfide
FT reductase (trxB) activity. No inhibition of SigR, no
FT diamide induction of SigR. Binds SigR in vitro."
FT /evidence="ECO:0000269|PubMed:16819828,
FT ECO:0000269|PubMed:21685450"
FT MUTAGEN 38
FT /note="F->A: No inhibition of SigR, no diamide induction of
FT SigR."
FT /evidence="ECO:0000269|PubMed:21685450"
FT MUTAGEN 39
FT /note="E->A: Wild-type inhibition of SigR, more induction
FT by diamide."
FT /evidence="ECO:0000269|PubMed:21685450"
FT MUTAGEN 40
FT /note="E->A: Wild-type inhibition of SigR, more induction
FT by diamide."
FT /evidence="ECO:0000269|PubMed:21685450"
FT MUTAGEN 41
FT /note="C->A: No inhibition of SigR, no diamide induction of
FT SigR."
FT /evidence="ECO:0000269|PubMed:11251822,
FT ECO:0000269|PubMed:21685450"
FT MUTAGEN 41
FT /note="C->S: No sporulation, constitutive expression of
FT trxCp1, no binding of SigR."
FT /evidence="ECO:0000269|PubMed:11251822,
FT ECO:0000269|PubMed:21685450"
FT MUTAGEN 43
FT /note="P->A: Decreases basal levels of SigR and its
FT induction by diamide; may bind it more tightly."
FT /evidence="ECO:0000269|PubMed:21685450"
FT MUTAGEN 44
FT /note="C->A: No inhibition of SigR, no diamide induction of
FT SigR."
FT /evidence="ECO:0000269|PubMed:11251822,
FT ECO:0000269|PubMed:21685450"
FT MUTAGEN 44
FT /note="C->S: No sporulation, constitutive expression of
FT trxCp1, no binding of SigR."
FT /evidence="ECO:0000269|PubMed:11251822,
FT ECO:0000269|PubMed:21685450"
FT MUTAGEN 45
FT /note="L->A: Wild-type inhibition of SigR, more induction
FT by diamide."
FT /evidence="ECO:0000269|PubMed:21685450"
FT MUTAGEN 46
FT /note="E->A: Wild-type inhibition of SigR, more induction
FT by diamide."
FT /evidence="ECO:0000269|PubMed:21685450"
FT MUTAGEN 61
FT /note="C->S: No effect on sporulation, normal induction of
FT trxCp1."
FT /evidence="ECO:0000269|PubMed:11251822"
FT MUTAGEN 62
FT /note="C->S: Reduced sporulation, normal induction of
FT trxCp1, no binding of SigR."
FT /evidence="ECO:0000269|PubMed:11251822"
FT HELIX 11..24
FT /evidence="ECO:0007829|PDB:5FRF"
FT HELIX 28..31
FT /evidence="ECO:0007829|PDB:5FRF"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:5FRF"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:5FRH"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:5FRF"
FT HELIX 51..60
FT /evidence="ECO:0007829|PDB:5FRF"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:5FRF"
FT HELIX 71..75
FT /evidence="ECO:0007829|PDB:5FRF"
FT HELIX 77..84
FT /evidence="ECO:0007829|PDB:5FRF"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:5FRF"
FT STRAND 91..95
FT /evidence="ECO:0007829|PDB:5FRF"
SQ SEQUENCE 105 AA; 11681 MW; B89B9BDB8A7AD1B3 CRC64;
MSCGEPHETD CSEILDHLYE FLDKEMPDSD CVKFEHHFEE CSPCLEKYGL EQAVKKLVKR
CCGQDDVPGD LRAKVMGRLD LIRSGQSVPE HDVAAAPSSS APQES
