Lampel Ayala, Yaniv Oren, Berger Or, Bacharach Eran, Gazit Ehud, Frolow Felix
Molecular Microbiology and Biotechnology, Tel Aviv University, 69978 Tel Aviv, Israel.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Jun;69(Pt 6):602-6. doi: 10.1107/S1744309113011871. Epub 2013 May 23.
The Gag precursor is the major structural protein of the virion of human immunodeficiency virus-1 (HIV-1). Capsid protein (CA), a cleavage product of Gag, plays an essential role in virus assembly both in Gag-precursor multimerization and in capsid core formation. The carboxy-terminal domain (CTD) of CA contains 20 residues that are highly conserved across retroviruses and constitute the major homology region (MHR). Genetic evidence implies a role for the MHR in interactions between Gag precursors during the assembly of the virus, but the structural basis for this role remains elusive. This paper describes a novel triclinic structure of the HIV-1 CA CTD at 1.6 Å resolution with two canonical dimers of CA CTD in the asymmetric unit. The canonical dimers form a newly identified packing interface where interactions of four conserved MHR residues take place. This is the first structural indication that these MHR residues participate in the putative CTD-CTD interactions. These findings suggest that the molecules forming this novel interface resemble an intermediate structure that participates in the early steps of HIV-1 assembly. This interface may therefore provide a novel target for antiviral drugs.
Gag前体是人类免疫缺陷病毒1型（HIV-1）病毒体的主要结构蛋白。衣壳蛋白（CA）是Gag的裂解产物，在病毒组装过程中，无论是在Gag前体多聚化还是衣壳核心形成方面都起着至关重要的作用。CA的羧基末端结构域（CTD）包含20个在逆转录病毒中高度保守的残基，构成了主要同源区域（MHR）。遗传学证据表明MHR在病毒组装过程中Gag前体之间的相互作用中发挥作用，但其作用的结构基础仍然难以捉摸。本文描述了HIV-1 CA CTD在1.6 Å分辨率下的一种新型三斜结构，不对称单元中有两个CA CTD的典型二聚体。典型二聚体形成了一个新发现的堆积界面，四个保守的MHR残基在该界面发生相互作用。这是这些MHR残基参与假定的CTD-CTD相互作用的首个结构证据。这些发现表明，形成这个新界面的分子类似于参与HIV-1组装早期步骤的中间结构。因此，这个界面可能为抗病毒药物提供一个新靶点。
