4R26

Crystal structure of human Fab PGT124, a broadly neutralizing and potent HIV-1 neutralizing antibody

Summary for 4R26

• Entry DOI: 10.2210/pdb4r26/pdb
• Descriptor: PGR124-Light Chain, PGT124-Heavy Chain, GLYCEROL, ... (4 entities in total)
• Functional Keywords: immune system, igg fold, antibody, hiv-1 binding
• Biological source: Nomascus leucogenys (Northern white-cheeked gibbon); More
• Cellular location: Secreted : P0DOY3 P0DOX5
• Total number of polymer chains: 2
• Total formula weight: 48793.39

Authors

Garces, F.,Kong, L.,Wilson, I.A. (deposition date: 2014-08-08, release date: 2014-10-08, Last modification date: 2024-11-06)

Primary citation

Garces, F.,Sok, D.,Kong, L.,McBride, R.,Kim, H.J.,Saye-Francisco, K.F.,Julien, J.P.,Hua, Y.,Cupo, A.,Moore, J.P.,Paulson, J.C.,Ward, A.B.,Burton, D.R.,Wilson, I.A.
Structural Evolution of Glycan Recognition by a Family of Potent HIV Antibodies.
Cell(Cambridge,Mass.), 159:69-79, 2014

PubMed 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.

PubMed: 25259921
DOI: 10.1016/j.cell.2014.09.009

Experimental method

X-RAY DIFFRACTION (2.4969 Å)