4XAK

Crystal structure of potent neutralizing antibody m336 in complex with MERS Co-V RBD

Summary for 4XAK

• Entry DOI: 10.2210/pdb4xak/pdb
• Descriptor: Spike glycoprotein, Heavy chain of neutralizing antibody m336, Light chain of neutralizing antibody m336, ... (6 entities in total)
• Functional Keywords: mers-cov rbd, antibody m336, neutralization, immune system
• Biological source: Human coronavirus EMC (HCoV-EMC); More
• Cellular location: Spike protein S2: Virion membrane ; Single-pass type I membrane protein . Spike protein S1: Virion membrane ; Peripheral membrane protein : K9N5Q8
• Total number of polymer chains: 6
• Total formula weight: 155793.68

Authors

Zhou, T.,Dimtrov, D.S.,Ying, T. (deposition date: 2014-12-15, release date: 2015-08-26, Last modification date: 2024-10-30)

Primary citation

Ying, T.,Prabakaran, P.,Du, L.,Shi, W.,Feng, Y.,Wang, Y.,Wang, L.,Li, W.,Jiang, S.,Dimitrov, D.S.,Zhou, T.
Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody.
Nat Commun, 6:8223-8223, 2015

PubMed Abstract: The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (∼36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.

PubMed: 26370782
DOI: 10.1038/ncomms9223

Experimental method

X-RAY DIFFRACTION (2.45 Å)