Structural evolution of glycan recognition by a family of potent HIV antibodies.

TitleStructural evolution of glycan recognition by a family of potent HIV antibodies.
Publication TypeJournal Article
Year of Publication2014
AuthorsGarces F, Sok D, Kong L, McBride R, Kim HJ, Saye-Francisco KF, Julien J-P, Hua Y, Cupo A, Moore JP, Paulson JC, Ward AB, Burton DR, Wilson IA
JournalCell
Volume159
Issue1
Pagination69-79
Date Published09/25/2014
ISSN1097-4172
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.

DOI10.1016/j.cell.2014.09.009
Alternate JournalCell
PubMed ID25259921
PubMed Central IDPMC4278586
Grant ListP01 AI082362 / AI / NIAID NIH HHS / United States
P01 AI832362 / AI / NIAID NIH HHS / United States
P41RR001209 / RR / NCRR NIH HHS / United States
R01 AI033292 / AI / NIAID NIH HHS / United States
R01 AI084817 / AI / NIAID NIH HHS / United States
R01 AI084817 / AI / NIAID NIH HHS / United States
R01 AI332932 / AI / NIAID NIH HHS / United States
R37 AI036082 / AI / NIAID NIH HHS / United States
R37 AI36082 / AI / NIAID NIH HHS / United States
RR017573 / RR / NCRR NIH HHS / United States
U54 GM094586 / GM / NIGMS NIH HHS / United States
U54 GM094586 / GM / NIGMS NIH HHS / United States
UM1 AI00663 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
CHAVI-ID: 
1
Cover Picture: