EMD-16706

Single-particle
2.6 Å
EMD-16706 Deposition: 16/02/2023
Map released: 26/04/2023
Last modified: 24/07/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-16706

HIV-1 mature capsid hexamer from CA-IP6 CLPs, bound to Nup153 peptide

EMD-16706

Single-particle
2.6 Å
EMD-16706 Deposition: 16/02/2023
Map released: 26/04/2023
Last modified: 24/07/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Human immunodeficiency virus 1, Homo sapiens
Sample: HIV-1 Mature Capsid
Fitted models: 8cky (Avg. Q-score: 0.597)

Deposition Authors: Stacey JCV, Briggs JAG
Two structural switches in HIV-1 capsid regulate capsid curvature and host factor binding.
Stacey JCV, Tan A , Lu JM , James LC, Dick RA , Briggs JAG
(2023) PNAS , 120 , e2220557120 - e2220557120
PUBMED: 37040417
DOI: doi:10.1073/pnas.2220557120
ISSN: 1091-6490
ASTM: PNASA6
Abstract:
The mature HIV-1 capsid protects the viral genome and interacts with host proteins to travel from the cell periphery into the nucleus. To achieve this, the capsid protein, CA, constructs conical capsids from a lattice of hexamers and pentamers, and engages in and then relinquishes multiple interactions with cellular proteins in an orchestrated fashion. Cellular host factors including Nup153, CPSF6, and Sec24C engage the same pocket within CA hexamers. How CA assembles pentamers and hexamers of different curvatures, how CA oligomerization states or curvature might modulate host-protein interactions, and how binding of multiple cofactors to a single site is coordinated, all remain to be elucidated. Here, using single-particle cryoEM, we have determined the structure of the mature HIV-1 CA pentamer and hexamer from conical CA-IP6 polyhedra to ~3 Å resolution. We also determined structures of hexamers in the context of multiple lattice curvatures and number of pentamer contacts. Comparison of these structures, bound or not to host protein peptides, revealed two structural switches within HIV-1 CA that modulate peptide binding according to CA lattice curvature and whether CA is hexameric or pentameric. These observations suggest that the conical HIV-1 capsid has different host-protein binding properties at different positions on its surface, which may facilitate cell entry and represent an evolutionary advantage of conical morphology.