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TitleConformational landscape of HIV-1 Env from closed to fully open.
Journal, issue, pagesNat Commun, Year 2026
Publish dateFeb 24, 2026
AuthorsJiayan Cui / Zi Jie Lin / Sukanya Ghosh / Jianqiu Du / Roopak Sadeesh / David B Weiner / Jesper Pallesen /
PubMed AbstractThe molecular mechanism of HIV-1 entry into host cells is governed by dynamic conformational changes to its envelope glycoprotein (Env), which are triggered by the engagement of the host receptor CD4 ...The molecular mechanism of HIV-1 entry into host cells is governed by dynamic conformational changes to its envelope glycoprotein (Env), which are triggered by the engagement of the host receptor CD4 and coreceptors. Structural insights into these transitions have been advanced by cryo-electron tomography (cryo-ET), resolving Env structures in closed and multifarious open states within native membranes, and by cryo-electron microscopy (cryo-EM), which has provided atomic details of these states. In this study, we determine cryo-EM structures of soluble native-like Env in complex with antibody 3BC315, antibody b12, CD4, or a combination of 3BC315 and b12, capturing previously uncharacterized conformational states. Observing enhanced 3BC315 binding occupancy in the presence of b12, we investigate the cooperativity of these antibodies using mass photometry and neutralization assays. Integrating these states with the literature, we establish a classification framework for symmetric and asymmetric Env states, categorizing by their degree of openness and stepwise structural rearrangements. Our findings refine the mechanistic understanding of HIV-1 Env dynamics and provide a structural roadmap for targeting dynamic Env states to develop more potent vaccines and immunotherapies.
External linksNat Commun / PubMed:41735302
MethodsEM (single particle)
Resolution2.91 - 3.88 Å
Structure data

EMDB-49236, PDB-9nbt:
AMC008 v4.2 SOSIP Env trimer in complex with VRC01 and 35O22 Fabs
Method: EM (single particle) / Resolution: 2.91 Å

EMDB-49238, PDB-9nby:
AMC008 v4.2 SOSIP Env trimer in complex with PGT121, VRC01 and 3BC315 Fabs
Method: EM (single particle) / Resolution: 3.16 Å

EMDB-49239, PDB-9nc0:
AMC008 v4.2 SOSIP Env trimer in complex with b12 Fab
Method: EM (single particle) / Resolution: 3.88 Å

EMDB-49240, PDB-9nc3:
AMC008 v4.2 SOSIP Env trimer in complex with b12 and 3BC315 Fabs
Method: EM (single particle) / Resolution: 3.74 Å

EMDB-49241, PDB-9nc6:
AMC008 v4.2 SOSIP Env trimer in complex with two 3BC315 Fabs
Method: EM (single particle) / Resolution: 3.52 Å

EMDB-49242, PDB-9nc8:
AMC008 v4.2 SOSIP Env trimer in complex with one 3BC315 Fab
Method: EM (single particle) / Resolution: 3.55 Å

EMDB-70287, PDB-9oaj:
AMC008 v4.2 SOSIP Env trimer in complex with CD4 D1D2
Method: EM (single particle) / Resolution: 2.91 Å

EMDB-73342, PDB-9yqo:
AMC008 v4.2 SOSIP Env trimer in complex with PGT121 and VRC01 Fabs
Method: EM (single particle) / Resolution: 3.26 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / HIV-1 Envelope glycoprotein / broadly neutralizing antibodies / cluster of differentiation 4

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