6UUH

Crystal structure of broad and potent HIV-1 neutralizing antibody 438-B11

Summary for 6UUH

• Entry DOI: 10.2210/pdb6uuh/pdb
• Related: 6UTK
• Descriptor: B11 Fab Heavy Chain, B11 Fab Light Chain, Immunoglobulin G-binding protein G, ... (5 entities in total)
• Functional Keywords: v3 glycan supersite, human antibody, immune system, anti-hiv neutralizing antibody, viral protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 113812.88

Authors

Kumar, S.,Wilson, I.A. (deposition date: 2019-10-30, release date: 2020-09-23, Last modification date: 2024-10-23)

Primary citation

Kumar, S.,Ju, B.,Shapero, B.,Lin, X.,Ren, L.,Zhang, L.,Li, D.,Zhou, Z.,Feng, Y.,Sou, C.,Mann, C.J.,Hao, Y.,Sarkar, A.,Hou, J.,Nunnally, C.,Hong, K.,Wang, S.,Ge, X.,Su, B.,Landais, E.,Sok, D.,Zwick, M.B.,He, L.,Zhu, J.,Wilson, I.A.,Shao, Y.
A V H 1-69 antibody lineage from an infected Chinese donor potently neutralizes HIV-1 by targeting the V3 glycan supersite.
Sci Adv, 6:-, 2020

PubMed Abstract: An oligomannose patch around the V3 base of HIV-1 envelope glycoprotein (Env) is recognized by multiple classes of broadly neutralizing antibodies (bNAbs). Here, we investigated the bNAb response to the V3 glycan supersite in an HIV-1-infected Chinese donor by Env-specific single B cell sorting, structural and functional studies, and longitudinal analysis of antibody and virus repertoires. Monoclonal antibodies 438-B11 and 438-D5 were isolated that potently neutralize HIV-1 with moderate breadth, are encoded by the V1-69 germline gene, and have a disulfide-linked long HCDR3 loop. Crystal structures of Env-bound and unbound antibodies revealed heavy chain-mediated recognition of the glycan supersite with a unique angle of approach and a critical role of the intra-HCDR3 disulfide. The mechanism of viral escape was examined via single-genome amplification/sequencing and glycan mutations around the N332 supersite. Our findings further emphasize the V3 glycan supersite as a prominent target for Env-based vaccine design.

PubMed: 32938661
DOI: 10.1126/sciadv.abb1328

Experimental method

X-RAY DIFFRACTION (2.7 Å)