人类免疫缺陷病毒1型整合酶N端锌结合结构域的溶液结构

Solution structure of the N-terminal zinc binding domain of HIV-1 integrase.

作者信息

Cai M, Zheng R, Caffrey M, Craigie R, Clore G M, Gronenborn A M

机构信息

Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.

出版信息

Nat Struct Biol. 1997 Jul;4(7):567-77. doi: 10.1038/nsb0797-567.

DOI:10.1038/nsb0797-567

PMID:9228950

Abstract

The solution structure of the N-terminal zinc binding domain (residues 1-55; IN1-55) of HIV-1 integrase has been solved by NMR spectroscopy. IN1-55 is dimeric, and each monomer comprises four helices with the zinc tetrahedrally coordinated to His 12, His 16, Cys 40 and Cys 43. IN1-55 exists in two interconverting conformational states that differ with regard to the coordination of the two histidine side chains to zinc. The different histidine arrangements are associated with large conformational differences in the polypeptide backbone (residues 9-18) around the coordinating histidines. The dimer interface is predominantly hydrophobic and is formed by the packing of the N-terminal end of helix 1, and helices 3 and 4. The monomer fold is remarkably similar to that of a number of helical DNA binding proteins containing a helix-turn-helix (HTH) motif with helices 2 and 3 of IN1-55 corresponding to the HTH motif. In contrast to the DNA binding proteins where the second helix of the HTH motif is employed for DNA recognition, IN1-55 uses this helix for dimerization.

摘要

通过核磁共振光谱法已解析出HIV-1整合酶N端锌结合结构域（残基1-55；IN1-55）的溶液结构。IN1-55是二聚体，每个单体包含四个螺旋，锌与组氨酸12、组氨酸16、半胱氨酸40和半胱氨酸43呈四面体配位。IN1-55以两种相互转换的构象状态存在，这两种状态在两个组氨酸侧链与锌的配位方面有所不同。不同的组氨酸排列与配位组氨酸周围多肽主链（残基9-18）的大构象差异相关。二聚体界面主要是疏水的，由螺旋1的N端以及螺旋3和螺旋4堆积形成。单体折叠与许多含有螺旋-转角-螺旋（HTH）基序的螺旋DNA结合蛋白非常相似，IN1-55的螺旋2和螺旋3对应于HTH基序。与HTH基序的第二个螺旋用于DNA识别的DNA结合蛋白不同，IN1-55利用这个螺旋进行二聚化。