5d1x

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IsdB NEAT2 bound by D4-30

Structural highlights

5d1x is a 5 chain structure with sequence from Homo sapiens and Staphylococcus aureus subsp. aureus USA300. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.21Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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References

  1. 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

Contents


PDB ID 5d1x

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