Structural Convergence between Cryo-EM and NMR Reveals Intersubunit Interactions Critical for HIV-1 Capsid Function

被引：211

作者：

Byeon, In-Ja L. ^{[1
]}

Meng, Xin ^{[1
]}

Jung, Jinwon ^{[1
]}

Zhao, Gongpu ^{[1
]}

Yang, Ruifeng ^{[2
]}

Ahn, Jinwoo ^{[1
]}

Shi, Jiong ^{[2
]}

Concel, Jason ^{[1
]}

Aiken, Christopher ^{[2
]}

Zhang, Peijun ^{[1
]}

Gronenborn, Angela M. ^{[1
]}

机构：

[1] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA

[2] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA

来源：

CELL | 2009年 / 139卷 / 04期

基金：

美国国家卫生研究院;

关键词：

C-TERMINAL DOMAIN; DIMERIZATION DOMAIN; CRYSTAL-STRUCTURES; MEMBRANE-PROTEINS; TUBULAR CRYSTALS; GAG POLYPROTEIN; VIRUS; RESOLUTION; ALIGNMENT; RECONSTRUCTIONS;

D O I：

10.1016/j.cell.2009.10.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mature HIV-1 particles contain conical-shaped capsids that enclose the viral RNA genome and perform essential functions in the virus life cycle. Previous structural analysis of two-and three-dimensional arrays of the capsid protein (CA) hexamer revealed three interfaces. Here, we present a cryoEM study of a tubular assembly of CA and a high-resolution NMR structure of the CA C-terminal domain (CTD) dimer. In the solution dimer structure, the monomers exhibit different relative orientations compared to previous X-ray structures. The solution structure fits well into the EM density map, suggesting that the dimer interface is retained in the assembled CA. We also identified a CTD-CTD interface at the local three-fold axis in the cryoEM map and confirmed its functional importance by mutagenesis. In the tubular assembly, CA intermolecular interfaces vary slightly, accommodating the asymmetry present in tubes. This provides the necessary plasticity to allow for controlled virus capsid dis/assembly.

引用

页码：780 / 790

页数：11

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