4R2G

Crystal Structure of PGT124 Fab bound to HIV-1 JRCSF gp120 core and to CD4

Summary for 4R2G

• Entry DOI: 10.2210/pdb4r2g/pdb
• Related: 4R26
• Descriptor: Surface protein gp160, T-cell surface glycoprotein CD4, PGT124 Light Chain, ... (9 entities in total)
• Functional Keywords: protein-protein complex, igg, anti-hiv antibodies, gp120, immune system
• Biological source: Human immunodeficiency virus type 1 group M subtype B (HIV-1); More
• Total number of polymer chains: 16
• Total formula weight: 428760.14

Authors

Garces, F.,Wilson, I.A. (deposition date: 2014-08-11, release date: 2014-10-08, Last modification date: 2024-12-25)

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 (3.283 Å)