ISDB_STAAN
ID ISDB_STAAN Reviewed; 645 AA.
AC Q7A656;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, 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=SA0976;
OS Staphylococcus aureus (strain N315).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=158879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=N315;
RX PubMed=11418146; DOI=10.1016/s0140-6736(00)04403-2;
RA Kuroda M., Ohta T., Uchiyama I., Baba T., Yuzawa H., Kobayashi I., Cui L.,
RA Oguchi A., Aoki K., Nagai Y., Lian J.-Q., Ito T., Kanamori M.,
RA Matsumaru H., Maruyama A., Murakami H., Hosoyama A., Mizutani-Ui Y.,
RA Takahashi N.K., Sawano T., Inoue R., Kaito C., Sekimizu K., Hirakawa H.,
RA Kuhara S., Goto S., Yabuzaki J., Kanehisa M., Yamashita A., Oshima K.,
RA Furuya K., Yoshino C., Shiba T., Hattori M., Ogasawara N., Hayashi H.,
RA Hiramatsu K.;
RT "Whole genome sequencing of meticillin-resistant Staphylococcus aureus.";
RL Lancet 357:1225-1240(2001).
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, DOMAIN, AND INTERACTION WITH HOST HBA.
RX PubMed=24645787; DOI=10.1021/bi500230f;
RA Bowden C.F., Verstraete M.M., Eltis L.D., Murphy M.E.;
RT "Hemoglobin binding and catalytic heme extraction by IsdB near iron
RT transporter domains.";
RL Biochemistry 53:2286-2294(2014).
RN [4] {ECO:0007744|PDB:3RTL, ECO:0007744|PDB:3RUR}
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 341-459 IN COMPLEX WITH HEME,
RP MUTAGENESIS OF SER-361; TYR-440 AND TYR-444, AND FUNCTION.
RX PubMed=21574663; DOI=10.1021/bi200369p;
RA Gaudin C.F., Grigg J.C., Arrieta A.L., Murphy M.E.;
RT "Unique heme-iron coordination by the hemoglobin receptor IsdB of
RT Staphylococcus aureus.";
RL Biochemistry 50:5443-5452(2011).
RN [5] {ECO:0007744|PDB:5VMM}
RP X-RAY CRYSTALLOGRAPHY (3.60 ANGSTROMS) OF 126-459 AND 126-265, FUNCTION,
RP INTERACTION WITH HOST HBA, AND MUTAGENESIS OF TYR-440 AND TYR-444.
RX PubMed=29109153; DOI=10.1074/jbc.m117.806562;
RA Bowden C.F.M., Chan A.C.K., Li E.J.W., Arrieta A.L., Eltis L.D.,
RA Murphy M.E.P.;
RT "Structure-function analyses reveal key features in Staphylococcus aureus
RT IsdB-associated unfolding of the heme-binding pocket of human hemoglobin.";
RL J. Biol. Chem. 293:177-190(2018).
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:24645787). 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 (PubMed:24645787,
CC PubMed:21574663, PubMed:29109153). Promotes also resistance to hydrogen
CC peroxide and killing by neutrophils (By similarity).
CC {ECO:0000250|UniProtKB:Q8NX66, ECO:0000269|PubMed:21574663,
CC ECO:0000269|PubMed:24645787, ECO:0000269|PubMed:29109153}.
CC -!- SUBUNIT: Interacts with host HBA; this interaction allows heme
CC extraction as iron source. Interacts with IsdA (By similarity).
CC {ECO:0000250|UniProtKB:Q8NX66, ECO:0000269|PubMed:24645787,
CC ECO:0000269|PubMed:29109153}.
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. {ECO:0000250}.
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:24645787}.
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; BA000018; BAB42225.1; -; Genomic_DNA.
DR PIR; E89883; E89883.
DR RefSeq; WP_001041583.1; NC_002745.2.
DR PDB; 3RTL; X-ray; 1.45 A; A/B/C/D=341-459.
DR PDB; 3RUR; X-ray; 1.70 A; A/B/C/D=341-459.
DR PDB; 5VMM; X-ray; 3.60 A; E/F=126-459, H/J=126-265.
DR PDBsum; 3RTL; -.
DR PDBsum; 3RUR; -.
DR PDBsum; 5VMM; -.
DR AlphaFoldDB; Q7A656; -.
DR SMR; Q7A656; -.
DR EnsemblBacteria; BAB42225; BAB42225; BAB42225.
DR KEGG; sau:SA0976; -.
DR HOGENOM; CLU_016167_0_0_9; -.
DR OMA; KADNNTY; -.
DR EvolutionaryTrace; Q7A656; -.
DR PRO; PR:Q7A656; -.
DR Proteomes; UP000000751; 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_0000292577"
FT PROPEP 614..645
FT /note="Removed by sortase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT /id="PRO_0000292578"
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..110
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:0000269|PubMed:21574663,
FT ECO:0007744|PDB:3RTL"
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:0000269|PubMed:21574663,
FT ECO:0007744|PDB:3RTL, ECO:0007744|PDB:3RUR"
FT MOD_RES 613
FT /note="Pentaglycyl murein peptidoglycan amidated threonine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT MUTAGEN 361
FT /note="S->A: Severe heme binding disruption."
FT /evidence="ECO:0000269|PubMed:21574663"
FT MUTAGEN 440
FT /note="Y->A: Severe heme binding disruption."
FT /evidence="ECO:0000269|PubMed:21574663"
FT MUTAGEN 440
FT /note="Y->F: Complete loss of heme transfer; in association
FT with F-444."
FT /evidence="ECO:0000269|PubMed:29109153"
FT MUTAGEN 444
FT /note="Y->A: Severe heme binding disruption."
FT /evidence="ECO:0000269|PubMed:21574663"
FT MUTAGEN 444
FT /note="Y->F: Complete loss of heme transfer; in association
FT with F-440."
FT /evidence="ECO:0000269|PubMed:29109153"
FT STRAND 343..347
FT /evidence="ECO:0007829|PDB:3RTL"
FT STRAND 350..360
FT /evidence="ECO:0007829|PDB:3RTL"
FT HELIX 362..366
FT /evidence="ECO:0007829|PDB:3RTL"
FT STRAND 372..376
FT /evidence="ECO:0007829|PDB:3RTL"
FT STRAND 379..388
FT /evidence="ECO:0007829|PDB:3RTL"
FT HELIX 389..391
FT /evidence="ECO:0007829|PDB:3RTL"
FT STRAND 392..397
FT /evidence="ECO:0007829|PDB:3RTL"
FT STRAND 403..408
FT /evidence="ECO:0007829|PDB:3RTL"
FT TURN 409..412
FT /evidence="ECO:0007829|PDB:3RTL"
FT STRAND 413..419
FT /evidence="ECO:0007829|PDB:3RTL"
FT STRAND 426..435
FT /evidence="ECO:0007829|PDB:3RTL"
FT HELIX 436..438
FT /evidence="ECO:0007829|PDB:3RTL"
FT STRAND 440..450
FT /evidence="ECO:0007829|PDB:3RTL"
FT HELIX 453..457
FT /evidence="ECO:0007829|PDB:3RTL"
SQ SEQUENCE 645 AA; 72162 MW; 524BF70EC0C4F9D8 CRC64;
MNKQQKEFKS FYSIRKSSLG VASVAISTLL LLMSNGEAQA AAEETGGTNT EAQPKTEAVA
SPTTTSEKAP ETKPVANAVS VSNKEVEAPT SETKEAKEVK EVKAPKETKA VKPAAKATNN
TYPILNQELR EAIKNPAIKD KDHSAPNSRP IDFEMKKENG EQQFYHYASS 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
