Crystal structure of cyclophilin A complexed with a binding site peptide from the HIV-1 capsid protein.
Crystal structure of cyclophilin A complexed with a binding site peptide from the HIV-1 capsid protein.
复制标题
亲环蛋白 A 与 HIV-1 衣壳蛋白结合位点肽复合的晶体结构。
DOI：
10.1002/pro.5560061103
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Hill,CP
中科院分区：
文献类型：
--
作者：
Vajdos,FF;Yoo,S;Houseweart,M;Sundquist,WI;Hill,CP
细胞蛋白亲环蛋白A（CypA）通过与病毒Gag多聚蛋白的衣壳结构域直接相互作用掺入1型人类免疫缺陷病毒（HIV-1）的病毒体中。我们证明了衣壳序列87 His-Ala-Gly-Pro-Ile-Ala 92（87 HAGPIA 92）包含主要亲环素A结合位点，并呈现CypA/HAGPIA复合物的X射线晶体结构。与所有先前报道的CypA与模型肽复合的结构中观察到的thecisprolines相反，该肽中的脯氨酸Pro 90以反式构象结合亲环素A活性位点。我们还报道了CypA和六肽HVGPIA之间的复合物的晶体结构，该复合物也保持了反式构象。与最近确定的CypA与HIV-1衣壳蛋白较大片段复合物的结构比较表明，CypA对这些六肽的识别涉及与肽残基Ala（瓦尔）88、Gly 89和Pro 90的接触，并且与较长序列的背景无关。
The cellular protein, cyclophilin A (CypA), is incorporated into the virion of the type 1 human immunodeficiency virus (HIV‐1) via a direct interaction with the capsid domain of the viral Gag polyprotein. We demonstrate that the capsid sequence87His‐Ala‐Gly‐Pro‐Ile‐Ala92(87HAGPIA92) encompasses the primary cyclophilin A binding site and present an X‐ray crystal structure of the CypA/HAGPIA complex. In contrast to thecisprolines observed in all previously reported structures of CypA complexed with model peptides, the proline in this peptide, Pro 90, binds the cyclophilin A active site in atransconformation. We also report the crystal structure of a complex between CypA and the hexapeptide HVGPIA, which also maintains thetransconformation. Comparison with the recently determined structures of CypA in complexes with larger fragments of the HIV‐1 capsid protein demonstrates that CypA recognition of these hexapeptides involves contacts with peptide residues Ala(Val) 88, Gly 89, and Pro 90, and is independent of the context of longer sequences.