8G6N

HIV-1 capsid lattice bound to dNTPs

8G6N の概要

• エントリーDOI: 10.2210/pdb8g6n/pdb
• EMDBエントリー: 29775
• 分子名称: Capsid protein (1 entity in total)
• 機能のキーワード: hiv-1, capsid, lattice, virus, virus like particle
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 186133.54

構造登録者

Highland, C.M.,Dick, R.A. (登録日: 2023-02-15, 公開日: 2023-05-03, 最終更新日: 2024-06-19)

主引用文献

Highland, C.M.,Tan, A.,Ricana, C.L.,Briggs, J.A.G.,Dick, R.A.
Structural insights into HIV-1 polyanion-dependent capsid lattice formation revealed by single particle cryo-EM.
Proc.Natl.Acad.Sci.USA, 120:e2220545120-e2220545120, 2023

PubMed Abstract: The HIV-1 capsid houses the viral genome and interacts extensively with host cell proteins throughout the viral life cycle. It is composed of capsid protein (CA), which assembles into a conical fullerene lattice composed of roughly 200 CA hexamers and 12 CA pentamers. Previous structural analyses of individual CA hexamers and pentamers have provided valuable insight into capsid structure and function, but detailed structural information about these assemblies in the broader context of the capsid lattice is lacking. In this study, we combined cryoelectron tomography and single particle analysis (SPA) cryoelectron microscopy to determine structures of continuous regions of the capsid lattice containing both hexamers and pentamers. We also developed a method of liposome scaffold-based in vitro lattice assembly ("lattice templating") that enabled us to directly study the lattice under a wider range of conditions than has previously been possible. Using this approach, we identified a critical role for inositol hexakisphosphate in pentamer formation and determined the structure of the CA lattice bound to the capsid-targeting antiretroviral drug GS-6207 (lenacapavir). Our work reveals key structural details of the mature HIV-1 CA lattice and establishes the combination of lattice templating and SPA as a robust strategy for studying retroviral capsid structure and capsid interactions with host proteins and antiviral compounds.

PubMed: 37094124
DOI: 10.1073/pnas.2220545120

実験手法

ELECTRON MICROSCOPY (3.5 Å)