3U2S

Crystal Structure of PG9 Fab in Complex with V1V2 Region from HIV-1 strain ZM109

Summary for 3U2S

• Entry DOI: 10.2210/pdb3u2s/pdb
• Related: 3U36
• Descriptor: PG9 heavy chain, PG9 light chain, Envelope glycoprotein gp120, ... (8 entities in total)
• Functional Keywords: greek key, immunoglobulin, immune recognition, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 130613.95

Authors

McLellan, J.S.,Pancera, M.,Kwong, P.D. (deposition date: 2011-10-04, release date: 2011-11-30, Last modification date: 2023-12-06)

Primary citation

McLellan, J.S.,Pancera, M.,Carrico, C.,Gorman, J.,Julien, J.P.,Khayat, R.,Louder, R.,Pejchal, R.,Sastry, M.,Dai, K.,O'Dell, S.,Patel, N.,Shahzad-Ul-Hussan, S.,Yang, Y.,Zhang, B.,Zhou, T.,Zhu, J.,Boyington, J.C.,Chuang, G.Y.,Diwanji, D.,Georgiev, I.,Do Kwon, Y.,Lee, D.,Louder, M.K.,Moquin, S.,Schmidt, S.D.,Yang, Z.Y.,Bonsignori, M.,Crump, J.A.,Kapiga, S.H.,Sam, N.E.,Haynes, B.F.,Burton, D.R.,Koff, W.C.,Walker, L.M.,Phogat, S.,Wyatt, R.,Orwenyo, J.,Wang, L.X.,Arthos, J.,Bewley, C.A.,Mascola, J.R.,Nabel, G.J.,Schief, W.R.,Ward, A.B.,Wilson, I.A.,Kwong, P.D.
Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9.
Nature, 480:336-343, 2011

PubMed Abstract: Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded β-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which-with PG9-involves a site of vulnerability comprising just two glycans and a strand.

PubMed: 22113616
DOI: 10.1038/nature10696

Experimental method

X-RAY DIFFRACTION (1.797 Å)