9I8I

cryoEM structure of HIV-1 KAKA/G225R mature CA hexamer

Summary for 9I8I

• Entry DOI: 10.2210/pdb9i8i/pdb
• EMDB information: 52724
• Descriptor: HIV-1 KAKA/G225R CA hexamer (1 entity in total)
• Functional Keywords: hiv-1, kaka/g225r, virus
• Biological source: HIV-1 06TG.HT008
• Total number of polymer chains: 6
• Total formula weight: 153686.19

Authors

Zhu, Y.,Shen, J.,Shen, Y.,Xu, J.,Zhang, P. (deposition date: 2025-02-05, release date: 2025-02-26, Last modification date: 2026-04-01)

Primary citation

Zhu, Y.,Kleinpeter, A.B.,Rey, J.S.,Shen, J.,Shen, Y.,Xu, J.,Hardenbrook, N.,Chen, L.,Lucic, A.,Perilla, J.R.,Freed, E.O.,Zhang, P.
Structural basis for HIV-1 capsid adaption to a deficiency in IP6 packaging.
Nat Commun, 16:8152-8152, 2025

PubMed Abstract: Inositol hexakisphosphate (IP6) promotes HIV-1 assembly by stabilizing the immature Gag lattice and becomes enriched within virions, where it is required for mature capsid assembly. Previously, we identified Gag mutants that package little IP6 yet assemble particles, though they are non-infectious due to defective capsid formation. Here, we report a compensatory mutation, G225R, in the C-terminus of capsid protein (CA) that restores capsid assembly and infectivity in these IP6-deficient mutants. G225R also enhances in vitro assembly of CA into capsid-like particles at far lower IP6 concentrations than required for wild-type CA. CryoEM structures of G225R CA hexamers and lattices at 2.7 Å resolution reveal that the otherwise disordered C-terminus becomes structured, stabilizing hexamer-hexamer interfaces. Molecular dynamics simulations support this mechanism. These findings uncover how HIV-1 can adapt to IP6 deficiency and highlight a previously unrecognized structural role of the CA C-terminus, while offering tools for capsid-related studies.

PubMed: 40890096
DOI: 10.1038/s41467-025-63363-9

Experimental method

ELECTRON MICROSCOPY (2.75 Å)