5D1X

IsdB NEAT2 bound by D4-30

Summary for 5D1X

• Entry DOI: 10.2210/pdb5d1x/pdb
• Related: 5D1Q 5D1Z
• Descriptor: D4-30 Light Chain, D4-30 Heavy Chain, P5 Heavy Chain, ... (5 entities in total)
• Functional Keywords: isdb, neat2, germline encoded, immune system
• Biological source: Homo sapiens; More
• Cellular location: Secreted, cell wall ; Peptidoglycan-anchor : Q2FHV2
• Total number of polymer chains: 5
• Total formula weight: 118809.07

Authors

Deng, X. (deposition date: 2015-08-04, release date: 2016-08-10, Last modification date: 2024-10-23)

Primary citation

Yeung, Y.A.,Foletti, D.,Deng, X.,Abdiche, Y.,Strop, P.,Glanville, J.,Pitts, S.,Lindquist, K.,Sundar, P.D.,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, 7:13376-13376, 2016

PubMed Abstract: 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.

PubMed: 27857134
DOI: 10.1038/ncomms13376

Experimental method

X-RAY DIFFRACTION (3.21 Å)