Faculty of Biology, Technion-Israel Institute of Technology, Haifa 320003, Israel.
Faculty of Biology, Technion-Israel Institute of Technology, Haifa 320003, Israel.
Structure. 2014 Oct 7;22(10):1512-9. doi: 10.1016/j.str.2014.08.001. Epub 2014 Sep 4.
Retroviral DNA integration into the host genome is mediated by nucleoprotein assemblies containing tetramers of viral integrase (IN). Whereas the fully active form of IN comprises a dimer of dimers, the molecular basis of IN multimerization has not been fully characterized. IN has consistently been crystallized in an analogous dimeric form in all crystallographic structures and experimental evidence as to the level of similarity between IN monomeric and dimeric conformations is missing because of the lack of IN monomeric structures. Here we identify Phe187 as a critical dimerization determinant of IN from feline immunodeficiency virus (FIV), a nonprimate lentivirus that causes AIDS in the natural host, and report, in addition to a canonical dimeric structure of the FIV IN core-domain, a monomeric structure revealing the preservation of the backbone structure between the two multimeric forms and suggest a role for Phe187 in "hinging" the flexible IN dimer.
逆转录病毒 DNA 整合到宿主基因组是由含有病毒整合酶（IN）四聚体的核蛋白组装体介导的。虽然完全活性形式的 IN 由二聚体组成，但 IN 多聚体形成的分子基础尚未完全表征。在所有晶体结构中，IN 都以类似二聚体的形式结晶，由于缺乏 IN 单体结构，因此关于 IN 单体和二聚体构象之间相似性的实验证据缺失。在这里，我们确定来自猫免疫缺陷病毒（FIV）的 IN 的苯丙氨酸 187 是关键的二聚化决定因素，FIV 是一种非灵长类慢病毒，在其自然宿主中会导致 AIDS，除了 FIV IN 核心结构域的典型二聚体结构外，我们还报告了单体结构，揭示了两种多聚体形式之间的骨架结构的保存，并提出了苯丙氨酸 187 在“铰链”柔性 IN 二聚体中的作用。
