5d1q
From Proteopedia
IsdB NEAT2 bound by clone D2-06
Structural highlights
Function[ISDB_STAAB] 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). Publication Abstract from PubMedStaphylococcus 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
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