Structural evolution of glycan recognition by a family of potent HIV antibodies Academic Article uri icon

Overview

MeSH Major

  • Antibodies, Neutralizing
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • HIV-1

abstract

  • The HIV envelope glycoprotein (Env) is densely covered with self-glycans that should help shield it from recognition by the human immune system. Here, we examine how a particularly potent family of broadly neutralizing antibodies (Abs) has evolved common and distinct structural features to counter the glycan shield and interact with both glycan and protein components of HIV Env. The inferred germline antibody already harbors potential binding pockets for a glycan and a short protein segment. Affinity maturation then leads to divergent evolutionary branches that either focus on a single glycan and protein segment (e.g., Ab PGT124) or engage multiple glycans (e.g., Abs PGT121-123). Furthermore, other surrounding glycans are avoided by selecting an appropriate initial antibody shape that prevents steric hindrance. Such molecular recognition lessons are important for engineering proteins that can recognize or accommodate glycans.

publication date

  • September 25, 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4278586

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2014.09.009

PubMed ID

  • 25259921

Additional Document Info

start page

  • 69

end page

  • 79

volume

  • 159

number

  • 1