7LPN

Cryo-EM structure of llama J3 VHH antibody in complex with HIV-1 Env BG505 DS-SOSIP.664

Summary for 7LPN

• Entry DOI: 10.2210/pdb7lpn/pdb
• EMDB information: 23480
• Descriptor: HIV-1 Envelope Glycoprotein BG505 SOSIP.664 gp41, Envelope glycoprotein gp160, J3 VHH, ... (8 entities in total)
• Functional Keywords: cd4, hiv-1, sosip, vaccine, immune system, llama, viral protein
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 9
• Total formula weight: 276485.27

Authors

Gorman, J.,Kwong, P.D. (deposition date: 2021-02-12, release date: 2022-02-23, Last modification date: 2024-11-06)

Primary citation

Zhou, T.,Chen, L.,Gorman, J.,Wang, S.,Kwon, Y.D.,Lin, B.C.,Louder, M.K.,Rawi, R.,Stancofski, E.D.,Yang, Y.,Zhang, B.,Quigley, A.F.,McCoy, L.E.,Rutten, L.,Verrips, T.,Weiss, R.A.,Doria-Rose, N.A.,Shapiro, L.,Kwong, P.D.
Structural basis for llama nanobody recognition and neutralization of HIV-1 at the CD4-binding site.
Structure, 30:862-875.e4, 2022

PubMed Abstract: Nanobodies can achieve remarkable neutralization of genetically diverse pathogens, including HIV-1. To gain insight into their recognition, we determined crystal structures of four llama nanobodies (J3, A12, C8, and D7), all of which targeted the CD4-binding site, in complex with the HIV-1 envelope (Env) gp120 core, and determined a cryoelectron microscopy (cryo-EM) structure of J3 with the Env trimer. Crystal and cryo-EM structures of J3 complexes revealed this nanobody to mimic binding to the prefusion-closed trimer for the primary site of CD4 recognition as well as a secondary quaternary site. In contrast, crystal structures of A12, C8, and D7 with gp120 revealed epitopes that included portions of the gp120 inner domain, inaccessible on the prefusion-closed trimer. Overall, these structures explain the broad and potent neutralization of J3 and limited neutralization of A12, C8, and D7, which utilized binding modes incompatible with the neutralization-targeted prefusion-closed conformation of Env.

PubMed: 35413243
DOI: 10.1016/j.str.2022.03.012

Experimental method

ELECTRON MICROSCOPY (3.61 Å)