8GPK

Crystal structure of human anti-HIV-1 broadly neutralizing antibody F6 Fab

This is a non-PDB format compatible entry.

Summary for 8GPK

• Entry DOI: 10.2210/pdb8gpk/pdb
• EMDB information: 34190 34192 34193 34194
• Descriptor: F6 Fab heavy Chain, F6 Fab light chain (2 entities in total)
• Functional Keywords: antibody, fab, hiv-1, env binding, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 98887.39

Authors

Niu, J.,Yang, B. (deposition date: 2022-08-26, release date: 2023-08-09, Last modification date: 2023-08-30)

Primary citation

Niu, J.,Wang, Q.,Zhao, W.,Meng, B.,Xu, Y.,Zhang, X.,Feng, Y.,Qi, Q.,Hao, Y.,Zhang, X.,Liu, Y.,Xiang, J.,Shao, Y.,Yang, B.
Structures and immune recognition of Env trimers from two Asia prevalent HIV-1 CRFs.
Nat Commun, 14:4676-4676, 2023

PubMed Abstract: Structure-guided immunofocusing HIV-1 vaccine design entails a comprehensive understanding of Envs from diverse HIV-1 subtypes, including circulating recombinant forms (CRFs). Here, we present the cryo-EM structures of Envs from two Asia prevalent CRFs (CRF01_AE and CRF07_BC) at 3.0 and 3.5 Å. We compare the structures and glycosylation patterns of Envs from different subtypes and perform cross-clade statistical analyses to reveal the unique features of CRF01_AE V1 region, which are associated with the resistance to certain bNAbs. We also solve a 4.1 Å cryo-EM structure of CRF01_AE Env in complex with F6, the first bNAb from CRF01_AE-infected individuals. F6 recognizes a gp120-gp41 spanning epitope to allosterically destabilize the Env trimer apex and weaken inter-protomer packing, which in turn hinders the receptor binding and induces Env trimer disassembly, demonstrating a dual mechanism of neutralization. These findings broaden our understanding of CRF Envs and shed lights on immunofocusing HIV-1 vaccine design.

PubMed: 37542068
DOI: 10.1038/s41467-023-40321-x

Experimental method

X-RAY DIFFRACTION (3.34 Å)