9BTL

Cryo-EM structure of rhesus antibody 41328-a.01 in complex with HIV-1 Env BG505 DS-SOSIP

Summary for 9BTL

• Entry DOI: 10.2210/pdb9btl/pdb
• EMDB information: 44893
• Descriptor: Envelope glycoprotein Gp120, 2-acetamido-2-deoxy-beta-D-glucopyranose, Envelope glycoprotein Gp41, ... (10 entities in total)
• Functional Keywords: neutralizing antibody, hiv-1 v2 apex, shiv-elicited, viral protein, immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 8
• Total formula weight: 283205.23

Authors

Roark, R.S.,Shapiro, L.,Kwong, P.D. (deposition date: 2024-05-15, release date: 2025-05-21, Last modification date: 2025-10-01)

Primary citation

Roark, R.S.,Habib, R.,Gorman, J.,Li, H.,Connell, A.J.,Bonsignori, M.,Guo, Y.,Hogarty, M.P.,Olia, A.S.,Sowers, K.J.,Zhang, B.,Bibollet-Ruche, F.,Bylund, T.,Callaghan, S.,Carey, J.W.,Cerutti, G.,Harris, D.R.,He, W.,Lewis, E.,Liu, T.,Mason, R.D.,Qiao, Y.,Park, Y.,Rando, J.M.,Singh, A.,Wolff, J.J.,Lei, Q.P.,Louder, M.K.,Andrabi, R.,Doria-Rose, N.A.,Saunders, K.O.,Seaman, M.S.,Haynes, B.F.,Kulp, D.W.,Mascola, J.R.,Roederer, M.,Pierson, T.C.,Sheng, Z.,Hahn, B.H.,Shaw, G.M.,Kwong, P.D.,Shapiro, L.
Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies.
J.Exp.Med., 222:-, 2025

PubMed Abstract: Broadly neutralizing antibodies targeting the V2 apex of HIV-1 envelope are desired as vaccine design templates, but few have been described. Here, we report 11 lineages of V2 apex-neutralizing antibodies from simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and determine cryo-EM structures for 9. A single V2 apex-neutralizing lineage accounted for cross-clade breadth in most macaques, and somatic hypermutation relative to breadth was generally low, exemplified by antibody V033-a.01 with <5% nucleotide mutation and 37% breadth (208-strain panel). Envelope complex structures revealed eight different antibody classes (one multi-donor) and the complete repertoire of all five possible recognition topologies, recapitulating canonical human modes of apex insertion and C-strand hydrogen bonding. Despite this diversity in recognition, all rhesus-V2 apex antibodies were derived from reading frame two of the DH3-15*01 gene. Collectively, these results define-in rhesus-the structural and genetic basis of HIV-1 V2 apex recognition and demonstrate unprecedented structural plasticity of a highly selected immunogenetic element.

PubMed: 40824240
DOI: 10.1084/jem.20250638

Experimental method

ELECTRON MICROSCOPY (2.96 Å)