Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env

Nat Commun. 2015 Feb 5;6:6144. doi: 10.1038/ncomms7144.

Abstract

HIV's envelope glycoprotein (Env) is the sole target for neutralizing antibodies. The structures of many broadly neutralizing antibodies (bNAbs) in complex with truncated Env subunits or components have been reported. However, their interaction with the intact Env trimer, and the structural determinants that underlie neutralization resistance in this more native context are less well understood. Here we use hydrogen/deuterium exchange to examine the interactions between a panel of bNAbs and native-like Env trimers (SOSIP.664 trimers). Highly potent bNAbs cause only localized effects at their binding interface, while the binding of less potent antibodies is associated with elaborate changes throughout the trimer. In conjunction with binding kinetics, our results suggest that poorly neutralizing antibodies can only bind when the trimer transiently samples an open state. We propose that the kinetics of such opening motions varies among isolates, with Env from neutralization-sensitive viruses opening more frequently than Env from resistant viruses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / chemistry*
  • Antibodies, Neutralizing / genetics
  • Binding Sites
  • Deuterium Exchange Measurement
  • Epitopes / chemistry*
  • Epitopes / genetics
  • Gene Expression
  • HEK293 Cells
  • HIV-1 / chemistry
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • env Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors
  • env Gene Products, Human Immunodeficiency Virus / chemistry*
  • env Gene Products, Human Immunodeficiency Virus / genetics

Substances

  • Antibodies, Neutralizing
  • Epitopes
  • Recombinant Proteins
  • env Gene Products, Human Immunodeficiency Virus