National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI147890
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
5U54AI150472-09
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
U54AI170855-01
米国
National Science Foundation (NSF, United States)
DMR-1719875
米国
Medical Research Council (MRC, United Kingdom)
MC_UP_1201/16
英国
引用
ジャーナル: Proc Natl Acad Sci U S A / 年: 2023 タイトル: Structural insights into HIV-1 polyanion-dependent capsid lattice formation revealed by single particle cryo-EM. 著者: Carolyn M Highland / Aaron Tan / Clifton L Ricaña / John A G Briggs / Robert A Dick / 要旨: 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 ...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.
全体 : HIV-1 CA lattice bound to IP6 and Lenacapavir
全体
名称: HIV-1 CA lattice bound to IP6 and Lenacapavir
要素
複合体: HIV-1 CA lattice bound to IP6 and Lenacapavir
タンパク質・ペプチド: Capsid protein
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超分子 #1: HIV-1 CA lattice bound to IP6 and Lenacapavir
超分子
名称: HIV-1 CA lattice bound to IP6 and Lenacapavir / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: Highly-curved HIV-1 capsid (CA) lattice assembled on small unilamellar vesicles with inositol hexakisphosphate (IP6) and Lenacapavir at pH 7.4