Head-to-tail dimers and interdomain flexibility revealed by the crystal structure of HIV-1 capsid protein (p24) complexed with a monoclonal antibody Fab
Head-to-tail dimers and interdomain flexibility revealed by the crystal structure of HIV-1 capsid protein (p24) complexed with a monoclonal antibody Fab
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DOI：
10.1093/emboj/18.5.1124
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发表时间：
1999-03-01
期刊：
影响因子：
11.4
通讯作者：
Cusack, S
中科院分区：
文献类型：
--
作者：
Berthet-Colominas, C;Monaco, S;Cusack, S
HIV-1 衣壳蛋白 (p24) 的完整分子与识别 C 末端结构域表位的单克隆抗体片段复合的晶体结构已在 3 埃分辨率下测定。 p24 的螺旋 N 端和 C 端结构域通过延伸肽连接，形成总长度为 75 埃的灵活连接的哑铃形分子。使用的p24构建体是具有N端延伸的变体，在某种程度上模拟p24的Gag背景。我们观察到p24分子的新型头尾二聚体，其通过在N端和C端结构域之间形成实质性分子间界面而发生。与之前观察到的p24二聚体的比较表明，相同的残基和二级结构元件可以参与不同的界面，揭示了p24分子显着的粘性和可塑性，这些特性与结构域间的灵活性相结合，可能对病毒颗粒的组装和成熟很重要。之前旨在测试特定N-N和C-C同二聚体界面的诱变研究并没有完全区分观察到的N-C界面的可能性。
The crystal structure of an intact molecule of HIV-1 capsid protein (p24) in complex with a monoclonal antibody fragment recognizing an epitope on the C-terminal domain has been determined at 3 Angstrom resolution. The helical N- and C-terminal domains of p24 are linked by an extended peptide forming a flexibly linked dumb-bell-shaped molecule 75 Angstrom in overall length. The p24 construct used is a variant with an N-terminal extension that mimics to some extent the Gag context of p24, We observed a novel head-to-tail dimer of p24 molecules which occurs through the formation of a substantial intermolecular interface between the N- and C-terminal domains. Comparison with previously observed p24 dimers shows that the same residues and secondary structural elements can partake in different interfaces revealing a remarkable stickiness and plasticity of the p24 molecule, properties which, combined with the inter-domain flexibility, are presumably important in the assembly and maturation of viral particles, Previous mutagenesis studies designed to test specific N-N and C-C homodimer interfaces do not discriminate fully against the possibility of the observed N-C interface.