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-Structure paper
| タイトル | Structural basis for HIV-1 capsid adaption to a deficiency in IP6 packaging. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 8152, Year 2025 |
| 掲載日 | 2025年9月1日 |
著者 | Yanan Zhu / Alex B Kleinpeter / Juan S Rey / Juan Shen / Yao Shen / Jialu Xu / Nathan Hardenbrook / Long Chen / Anka Lucic / Juan R Perilla / Eric O Freed / Peijun Zhang / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:40890096 / PubMed Central |
| 手法 | EM (サブトモグラム平均) / EM (単粒子) |
| 解像度 | 2.75 - 4.24 Å |
| 構造データ | ![]() EMDB-51821: The structure from subtomogram averaging of HIV immature Gag with G225R mutation ![]() EMDB-51822: The structure from subtomogram averaging of HIV-1 immature Gag with KAKA/G225R mutations ![]() EMDB-51823: The structure from subtomogram averaging of HIV-1 immature Gag with KAKA/T8I/G225R mutations ![]() EMDB-51824: The structure from subtomogram averaging of HIV-1 immature Gag with A77V/KAKA/T8I/G225R mutations ![]() EMDB-51825: The structure from subtomogram averaging of HIV-1 immature Gag with KAKA/T8I mutations ![]() EMDB-51826: The structure from subtomogram averaging of HIV-1 Gag with K227A mutation EMDB-52724, PDB-9i8i: ![]() EMDB-52725: cryoEM structure of HIV-1 KAKA/G225R mature CA tri-hexamer in Class1 ![]() EMDB-52726: cryoEM structure of HIV-1 KAKA/G225R mature CA tri-hexamer in Class2 |
| 由来 |
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キーワード | VIRUS / HIV-1 / KAKA/G225R |
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hiv-1 06tg.ht008 (ヒト免疫不全ウイルス)
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