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Structure paper

TitleStructures and immune recognition of Env trimers from two Asia prevalent HIV-1 CRFs.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 4676, Year 2023
Publish dateAug 4, 2023
AuthorsJun Niu / Qi Wang / Wenwen Zhao / Bing Meng / Youwei Xu / Xianfang Zhang / Yi Feng / Qilian Qi / Yanling Hao / Xuan Zhang / Ying Liu / Jiangchao Xiang / Yiming Shao / Bei Yang /
PubMed AbstractStructure-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 ...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.
External linksNat Commun / PubMed:37542068 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.0 - 4.1 Å
Structure data

EMDB-34190, PDB-8gp5:
Structure of X18 UFO protomer in complex with F6 Fab VHVL domain
Method: EM (single particle) / Resolution: 4.05 Å

EMDB-34192, PDB-8gpg:
HIV-1 Env X18 UFO in complex with F6 Fab
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-34193, PDB-8gpi:
HIV-1 Env X18 UFO in complex with 8ANC195 Fab
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-34194, PDB-8gpj:
HIV-1 Env X16 UFO in complex with 8ANC195 Fab
Method: EM (single particle) / Resolution: 3.5 Å

PDB-8gpk:
Crystal structure of human anti-HIV-1 broadly neutralizing antibody F6 Fab
Method: X-RAY DIFFRACTION / Resolution: 3.34 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • homo sapiens (human)
  • human (human)
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN / Antibody / HIV-1 / Env protein / Complex / IMMUNE SYSTEM / Fab / Env binding

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