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-Structure paper
| タイトル | A molecular switch modulates assembly and host factor binding of the HIV-1 capsid. |
|---|---|
| ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 30, Issue 3, Page 383-390, Year 2023 |
| 掲載日 | 2023年2月9日 |
著者 | Randall T Schirra / Nayara F B Dos Santos / Kaneil K Zadrozny / Iga Kucharska / Barbie K Ganser-Pornillos / Owen Pornillos / ![]() |
| PubMed 要旨 | The HIV-1 capsid is a fullerene cone made of quasi-equivalent hexamers and pentamers of the viral CA protein. Typically, quasi-equivalent assembly of viral capsid subunits is controlled by a ...The HIV-1 capsid is a fullerene cone made of quasi-equivalent hexamers and pentamers of the viral CA protein. Typically, quasi-equivalent assembly of viral capsid subunits is controlled by a molecular switch. Here, we identify a Thr-Val-Gly-Gly motif that modulates CA hexamer/pentamer switching by folding into a 3 helix in the pentamer and random coil in the hexamer. Manipulating the coil/helix configuration of the motif allowed us to control pentamer and hexamer formation in a predictable manner, thus proving its function as a molecular switch. Importantly, the switch also remodels the common binding site for host factors that are critical for viral replication and the new ultra-potent HIV-1 inhibitor lenacapavir. This study reveals that a critical assembly element also modulates the post-assembly and viral replication functions of the HIV-1 capsid and provides new insights on capsid function and inhibition. |
リンク | Nat Struct Mol Biol / PubMed:36759579 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.2 - 3.9 Å |
| 構造データ | EMDB-26715, PDB-7urn: EMDB-26718, PDB-7urt: EMDB-28054, PDB-8eep: EMDB-28057, PDB-8eet: EMDB-28186, PDB-8ejl: |
| 化合物 | ![]() ChemComp-IHP: |
| 由来 |
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キーワード | VIRUS LIKE PARTICLE / HIV-1 / capsid / declination / pentamer / hexamer / VIRAL PROTEIN |
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human immunodeficiency virus 1 (ヒト免疫不全ウイルス)
homo sapiens (ヒト)
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