ISDB_STAAW
ID ISDB_STAAW Reviewed; 645 AA.
AC Q8NX66;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Iron-regulated surface determinant protein B;
DE AltName: Full=Fur-regulated protein B;
DE AltName: Full=Staphylococcal iron-regulated protein H;
DE AltName: Full=Staphylococcus aureus surface protein J;
DE Flags: Precursor;
GN Name=isdB; Synonyms=frpB, sasJ, sirH; OrderedLocusNames=MW1011;
OS Staphylococcus aureus (strain MW2).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=196620;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MW2;
RX PubMed=12044378; DOI=10.1016/s0140-6736(02)08713-5;
RA Baba T., Takeuchi F., Kuroda M., Yuzawa H., Aoki K., Oguchi A., Nagai Y.,
RA Iwama N., Asano K., Naimi T., Kuroda H., Cui L., Yamamoto K., Hiramatsu K.;
RT "Genome and virulence determinants of high virulence community-acquired
RT MRSA.";
RL Lancet 359:1819-1827(2002).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=17075065; DOI=10.1073/pnas.0606863103;
RA Stranger-Jones Y.K., Bae T., Schneewind O.;
RT "Vaccine assembly from surface proteins of Staphylococcus aureus.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:16942-16947(2006).
RN [3]
RP FUNCTION IN RESISTANCE TO INNATE HOST DEFENSE, AND INDUCTION.
RX PubMed=18097052; DOI=10.4049/jimmunol.180.1.500;
RA Palazzolo-Ballance A.M., Reniere M.L., Braughton K.R., Sturdevant D.E.,
RA Otto M., Kreiswirth B.N., Skaar E.P., DeLeo F.R.;
RT "Neutrophil microbicides induce a pathogen survival response in community-
RT associated methicillin-resistant Staphylococcus aureus.";
RL J. Immunol. 180:500-509(2008).
RN [4]
RP STRUCTURE BY NMR OF 125-272, FUNCTION, MUTAGENESIS OF PHE-164, AND DOMAIN.
RX PubMed=24871270; DOI=10.1021/bi5005188;
RA Fonner B.A., Tripet B.P., Eilers B.J., Stanisich J.,
RA Sullivan-Springhetti R.K., Moore R., Liu M., Lei B., Copie V.;
RT "Solution structure and molecular determinants of hemoglobin binding of the
RT first NEAT domain of IsdB in Staphylococcus aureus.";
RL Biochemistry 53:3922-3933(2014).
CC -!- FUNCTION: Cell wall-anchored surface receptor that extracts heme from
CC oxidized methemoglobin/metHb to enable growth on hemoglobin as a sole
CC iron source (PubMed:24871270). Rapidly extracts heme from hemoglobin
CC and transfers it to IsdA or IsdC, which then relays it to the membrane
CC transporter/IsdEF for internalization. Promotes also resistance to
CC hydrogen peroxide and killing by neutrophils (PubMed:18097052).
CC {ECO:0000269|PubMed:18097052, ECO:0000269|PubMed:24871270}.
CC -!- SUBUNIT: Interacts with host HBA; this interaction allows heme
CC extraction as iron source. Interacts with IsdA.
CC {ECO:0000250|UniProtKB:A6QG30}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000255|PROSITE-
CC ProRule:PRU00477}; Peptidoglycan-anchor {ECO:0000255|PROSITE-
CC ProRule:PRU00477}. Note=Anchored to the cell wall by sortase A (By
CC similarity). {ECO:0000250|UniProtKB:Q2FZF0}.
CC -!- INDUCTION: Repressed by fur in the presence of iron (By similarity).
CC Transcriptionally up-regulated by hydrogen peroxide and to a lesser
CC extent by hypochlorous acid. Slightly down-regulated by human
CC neutrophil azurophilic granule proteins. {ECO:0000250,
CC ECO:0000269|PubMed:18097052}.
CC -!- DOMAIN: The two NEAr transporter (NEAT) domains act in concert to bind,
CC extract, and transfer heme from hemoglobin to downstream Isd proteins.
CC {ECO:0000269|PubMed:24871270}.
CC -!- BIOTECHNOLOGY: A combined vaccine containing IsdA, IsdB, SdrD and SdrE
CC afforded significant protection in mice against a lethal challenge with
CC S.aureus Newman or any of the clinical isolates NRS252, N315, NRS248,
CC USA100 and USA400. The immune response elicited by the combined vaccine
CC is greater than the one elicited by its individual components.
CC {ECO:0000269|PubMed:17075065}.
CC -!- SIMILARITY: Belongs to the IsdB family. {ECO:0000305}.
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DR EMBL; BA000033; BAB94876.1; -; Genomic_DNA.
DR RefSeq; WP_001041586.1; NC_003923.1.
DR PDB; 2MOQ; NMR; -; A=125-272.
DR PDB; 7PCF; EM; 5.82 A; E/F=124-485.
DR PDB; 7PCH; EM; 2.89 A; E/F=124-485.
DR PDB; 7PCQ; EM; 3.62 A; E=124-485.
DR PDBsum; 2MOQ; -.
DR PDBsum; 7PCF; -.
DR PDBsum; 7PCH; -.
DR PDBsum; 7PCQ; -.
DR AlphaFoldDB; Q8NX66; -.
DR SMR; Q8NX66; -.
DR EnsemblBacteria; BAB94876; BAB94876; BAB94876.
DR KEGG; sam:MW1011; -.
DR HOGENOM; CLU_016167_0_0_9; -.
DR OMA; KADNNTY; -.
DR PRO; PR:Q8NX66; -.
DR Proteomes; UP000000418; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0015232; F:heme transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR CDD; cd06920; NEAT; 1.
DR Gene3D; 2.60.40.1850; -; 2.
DR InterPro; IPR019929; Iron-reg_IsdB.
DR InterPro; IPR019931; LPXTG_anchor.
DR InterPro; IPR006635; NEAT_dom.
DR InterPro; IPR037250; NEAT_dom_sf.
DR InterPro; IPR005877; YSIRK_signal_dom.
DR Pfam; PF00746; Gram_pos_anchor; 1.
DR Pfam; PF05031; NEAT; 2.
DR Pfam; PF04650; YSIRK_signal; 1.
DR SMART; SM00725; NEAT; 2.
DR SUPFAM; SSF158911; SSF158911; 2.
DR TIGRFAMs; TIGR03657; IsdB; 1.
DR TIGRFAMs; TIGR01168; YSIRK_signal; 1.
DR PROSITE; PS50847; GRAM_POS_ANCHORING; 1.
DR PROSITE; PS50978; NEAT; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Cell wall; Heme; Iron; Metal-binding; Peptidoglycan-anchor;
KW Repeat; Secreted; Signal; Virulence.
FT SIGNAL 1..40
FT /evidence="ECO:0000255"
FT CHAIN 41..613
FT /note="Iron-regulated surface determinant protein B"
FT /id="PRO_0000292575"
FT PROPEP 614..645
FT /note="Removed by sortase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT /id="PRO_0000292576"
FT DOMAIN 144..269
FT /note="NEAT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00337"
FT DOMAIN 341..458
FT /note="NEAT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00337"
FT REGION 38..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 458..619
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 12..23
FT /note="YSIRK-G/S signaling motif"
FT /evidence="ECO:0000250|UniProtKB:Q2FZF0"
FT MOTIF 610..614
FT /note="LPXTG sorting signal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT COMPBIAS 41..87
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 88..113
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 458..472
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 473..492
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 493..529
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 530..619
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 362
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q7A656"
FT BINDING 440
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q7A656"
FT MOD_RES 613
FT /note="Pentaglycyl murein peptidoglycan amidated threonine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT MUTAGEN 164
FT /note="F->D: Complete loss of binding to metHb."
FT /evidence="ECO:0000269|PubMed:24871270"
FT HELIX 129..132
FT /evidence="ECO:0007829|PDB:2MOQ"
FT TURN 136..138
FT /evidence="ECO:0007829|PDB:2MOQ"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:2MOQ"
FT STRAND 153..156
FT /evidence="ECO:0007829|PDB:2MOQ"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:2MOQ"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:2MOQ"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:2MOQ"
FT STRAND 184..190
FT /evidence="ECO:0007829|PDB:2MOQ"
FT TURN 192..194
FT /evidence="ECO:0007829|PDB:2MOQ"
FT STRAND 195..202
FT /evidence="ECO:0007829|PDB:2MOQ"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:2MOQ"
FT STRAND 209..215
FT /evidence="ECO:0007829|PDB:2MOQ"
FT TURN 216..219
FT /evidence="ECO:0007829|PDB:2MOQ"
FT STRAND 220..226
FT /evidence="ECO:0007829|PDB:2MOQ"
FT STRAND 231..242
FT /evidence="ECO:0007829|PDB:2MOQ"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:2MOQ"
FT STRAND 253..260
FT /evidence="ECO:0007829|PDB:2MOQ"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:2MOQ"
SQ SEQUENCE 645 AA; 72192 MW; C248D6CF84700B55 CRC64;
MNKQQKEFKS FYSIRKSSLG VASVAISTLL LLMSNGEAQA AAEETGGTNT EAQPKTEAVA
SPTTTSEKAP ETKPVANAVS VSNKEVEAPT SETKEAKEVK EVKAPKETKE VKPAAKATNN
TYPILNQELR EAIKNPAIKD KDHSAPNSRP IDFEMKKKDG TQQFYHYASS VKPARVIFTD
SKPEIELGLQ SGQFWRKFEV YEGDKKLPIK LVSYDTVKDY AYIRFSVSNG TKAVKIVSST
HFNNKEEKYD YTLMEFAQPI YNSADKFKTE EDYKAEKLLA PYKKAKTLER QVYELNKIQD
KLPEKLKAEY KKKLEDTKKA LDEQVKSAIT EFQNVQPTNE KMTDLQDTKY VVYESVENNE
SMMDTFVKHP IKTGMLNGKK YMVMETTNDD YWKDFMVEGQ RVRTISKDAK NNTRTIIFPY
VEGKTLYDAI VKVHVKTIDY DGQYHVRIVD KEAFTKANTD KSNKKEQQDN SAKKEATPAT
PSKPTPSPVE KESQKQDSQK DDNKQLPSVE KENDASSESG KDKTPATKPT KGEVESSSTT
PTKVVSTTQN VAKPTTASSK TTKDVVQTSA GSSEAKDSAP LQKANIKNTN DGHTQSQNNK
NTQENKAKSL PQTGEESNKD MTLPLMALLA LSSIVAFVLP RKRKN
