8TGU

Cryo-EM structure of BG505 SOSIP trimer purified via Galanthus nivalis lectin chromatography

Summary for 8TGU

• Entry DOI: 10.2210/pdb8tgu/pdb
• EMDB information: 41244
• Descriptor: HIV-1 Envelope glycoprotein BG505 SOSIP, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: hiv-1, glycoprotein, lectin, trimer, viral protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 3
• Total formula weight: 233006.49

Authors

Parsons, R.J.,Pothula, K.,Acharya, P. (deposition date: 2023-07-13, release date: 2024-08-28, Last modification date: 2024-11-13)

Primary citation

Parthasarathy, D.,Pothula, K.R.,Ratnapriya, S.,Cervera Benet, H.,Parsons, R.,Huang, X.,Sammour, S.,Janowska, K.,Harris, M.,Sodroski, J.,Acharya, P.,Herschhorn, A.
Conformational flexibility of HIV-1 envelope glycoproteins modulates transmitted/founder sensitivity to broadly neutralizing antibodies.
Nat Commun, 15:7334-7334, 2024

PubMed Abstract: HIV-1 envelope glycoproteins (Envs) of most primary HIV-1 strains exist in closed conformation and infrequently sample open states, limiting access to internal epitopes. Thus, immunogen design aims to mimic the closed Env conformation as preferred target for eliciting broadly neutralizing antibodies (bnAbs). Here we identify incompletely closed Env conformations of 6 out of 13 transmitted/founder (T/F) strains that are sensitive to antibodies that recognize internal epitopes typically exposed on open Envs. A 3.6 Å cryo-electron microscopy structure of unliganded, incompletely closed T/F Envs (1059-SOSIP) reveals protomer motion that increased sampling of states with incompletely closed trimer apex. We reconstruct de novo the post-transmission evolutionary pathway of a second T/F. Evolved viruses exhibit increased Env resistance to cold, soluble CD4 and 19b, all of which correlate with closing of the adapted Env trimer. Lastly, we show that the ultra-broad N6 bnAb efficiently recognizes different Env conformations and exhibits improved antiviral breadth against VRC01-resistant Envs isolated during the first-in-humans antibody-mediated-prevention trial.

PubMed: 39187497
DOI: 10.1038/s41467-024-51656-4

Experimental method

ELECTRON MICROSCOPY (3.8 Å)