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| | <StructureSection load='5d1x' size='340' side='right'caption='[[5d1x]], [[Resolution|resolution]] 3.21Å' scene=''> | | <StructureSection load='5d1x' size='340' side='right'caption='[[5d1x]], [[Resolution|resolution]] 3.21Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5d1x]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Staa3 Staa3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D1X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D1X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5d1x]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_USA300 Staphylococcus aureus subsp. aureus USA300]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D1X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5D1X FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5d1q|5d1q]], [[5d1z|5d1z]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.21Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">isdB, frpB, sasJ, sirH, SAUSA300_1028 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=367830 STAA3])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5d1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d1x OCA], [https://pdbe.org/5d1x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5d1x RCSB], [https://www.ebi.ac.uk/pdbsum/5d1x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5d1x ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5d1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d1x OCA], [http://pdbe.org/5d1x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d1x RCSB], [http://www.ebi.ac.uk/pdbsum/5d1x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5d1x ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ISDB_STAA3 ISDB_STAA3]] Seems to function as the primary receptor for hemoglobin since its inactivation inhibits the ability of S.aureus to bind hemoglobin. Binds hemoglobin in a dose-dependent way. Required for S.aureus growth using hemoglobin as the sole iron source. Also required for virulence. IsdA and/or IsdB promote resistance to hydrogen peroxide and killing by neutrophils (By similarity). | + | [https://www.uniprot.org/uniprot/ISDB_STAA8 ISDB_STAA8] Cell wall-anchored surface receptor that extracts heme from oxidized metHb to enable growth on hemoglobin as a sole iron source. Rapidly extracts heme from hemoglobin and transfers it to IsdA or IsdC, which then relays it to the membrane transporter/IsdEF for internalization. Promotes also resistance to hydrogen peroxide and killing by neutrophils.[UniProtKB:A6QG30] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Staa3]] | + | [[Category: Staphylococcus aureus subsp. aureus USA300]] |
| - | [[Category: Deng, X]] | + | [[Category: Deng X]] |
| - | [[Category: Germline encoded]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Isdb]]
| + | |
| - | [[Category: Neat2]]
| + | |
| Structural highlights
Function
ISDB_STAA8 Cell wall-anchored surface receptor that extracts heme from oxidized metHb to enable growth on hemoglobin as a sole iron source. Rapidly extracts heme from hemoglobin and transfers it to IsdA or IsdC, which then relays it to the membrane transporter/IsdEF for internalization. Promotes also resistance to hydrogen peroxide and killing by neutrophils.[UniProtKB:A6QG30]
Publication Abstract from PubMed
Staphylococcus aureus is both an important pathogen and a human commensal. To explore this ambivalent relationship between host and microbe, we analysed the memory humoral response against IsdB, a protein involved in iron acquisition, in four healthy donors. Here we show that in all donors a heavily biased use of two immunoglobulin heavy chain germlines generated high affinity (pM) antibodies that neutralize the two IsdB NEAT domains, IGHV4-39 for NEAT1 and IGHV1-69 for NEAT2. In contrast to the typical antibody/antigen interactions, the binding is primarily driven by the germline-encoded hydrophobic CDRH-2 motifs of IGHV1-69 and IGHV4-39, with a binding mechanism nearly identical for each antibody derived from different donors. Our results suggest that IGHV1-69 and IGHV4-39, while part of the adaptive immune system, may have evolved under selection pressure to encode a binding motif innately capable of recognizing and neutralizing a structurally conserved protein domain involved in pathogen iron acquisition.
Germline-encoded neutralization of a Staphylococcus aureus virulence factor by the human antibody repertoire.,Yeung YA, Foletti D, Deng X, Abdiche Y, Strop P, Glanville J, Pitts S, Lindquist K, Sundar PD, Sirota M, Hasa-Moreno A, Pham A, Melton Witt J, Ni I, Pons J, Shelton D, Rajpal A, Chaparro-Riggers J Nat Commun. 2016 Nov 18;7:13376. doi: 10.1038/ncomms13376. PMID:27857134[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yeung YA, Foletti D, Deng X, Abdiche Y, Strop P, Glanville J, Pitts S, Lindquist K, Sundar PD, Sirota M, Hasa-Moreno A, Pham A, Melton Witt J, Ni I, Pons J, Shelton D, Rajpal A, Chaparro-Riggers J. Germline-encoded neutralization of a Staphylococcus aureus virulence factor by the human antibody repertoire. Nat Commun. 2016 Nov 18;7:13376. doi: 10.1038/ncomms13376. PMID:27857134 doi:http://dx.doi.org/10.1038/ncomms13376
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