9D90

Cryo-EM structure of partially open HIV-1 BG505 SOSIP.664 Env bound to 3-sCD4, 3-17b Fab and 3-VRC34.01 Fab, Population 1

Summary for 9D90

• Entry DOI: 10.2210/pdb9d90/pdb
• EMDB information: 46653 46655
• Descriptor: Surface protein gp120, Transmembrane protein gp41, VRC34.01 heavy chain, ... (9 entities in total)
• Functional Keywords: recombinantly purified hiv-1 env, scd4, 17b fab and vrc34.01 fab, viral env, vaccine, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 21
• Total formula weight: 555893.99

Authors

Thakur, B.,Acharya, P. (deposition date: 2024-08-20, release date: 2025-04-30, Last modification date: 2025-10-01)

Primary citation

Thakur, B.,Katte, R.H.,Xu, W.,Janowska, K.,Sammour, S.,Henderson, R.,Lu, M.,Kwong, P.D.,Acharya, P.
Conformational trajectory of the HIV-1 fusion peptide during CD4-induced envelope opening.
Nat Commun, 16:4595-4595, 2025

PubMed Abstract: The hydrophobic fusion peptide (FP), a critical component of the HIV-1 entry machinery, is located at the N terminus of the envelope (Env) gp41 subunit. The receptor-binding gp120 subunit of Env forms a heterodimer with gp41. The gp120/gp41 heterodimer assembles into a homotrimer, in which FP is accessible for antibody binding. Env conformational changes or "opening" that follow receptor binding result in FP relocating to a newly formed interprotomer pocket at the gp41-gp120 interface where it is sterically inaccessible to antibodies. The mechanistic steps connecting the entry-related transition of antibody accessible-to-inaccessible FP configurations remain unresolved. Here, using SOSIP-stabilized Env ectodomains, we visualize that the FP remains accessible for antibody binding despite substantial receptor-induced Env opening. We delineate stepwise Env opening from its closed state to a functional CD4-bound symmetrically open Env in which we show that FP was accessible for antibody binding. We define downstream re-organizations that lead to the formation of a gp120/gp41 cavity into which the FP buries to become inaccessible for antibody binding. These findings improve our understanding of HIV-1 entry and delineate the entry-related conformational trajectory of a key site of HIV vulnerability to neutralizing antibody.

PubMed: 40382314
DOI: 10.1038/s41467-025-59721-2

Experimental method

ELECTRON MICROSCOPY (3.91 Å)