Mische Claudia C, Yuan Wen, Strack Bettina, Craig Stewart, Farzan Michael, Sodroski Joseph
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Virology. 2005 Jul 20;338(1):133-43. doi: 10.1016/j.virol.2005.05.001.
The human immunodeficiency virus (HIV-1) transmembrane envelope glycoprotein, gp41, which mediates virus-cell fusion, exists in at least three different conformations within the trimeric envelope glycoprotein complex. The structures of the prefusogenic and intermediate states are unknown; structures representing the postfusion state have been solved. In the postfusion conformation, three helical heptad repeat 2 (HR2) regions pack in an antiparallel fashion into the hydrophobic grooves on the surface of a triple-helical coiled coil formed by the heptad repeat 1 (HR1) regions. We studied the prefusogenic conformation of gp41 by mutagenic alteration of membrane-anchored and soluble forms of the HIV-1 envelope glycoproteins. Our results indicate that, in the HIV-1 envelope glycoprotein precursor, the gp41 HR1 region is in a conformation distinct from that of a trimeric coiled coil. Thus, the central gp41 coiled coil is formed during the transition of the HIV-1 envelope glycoproteins from the precursor state to the receptor-bound intermediate.
人类免疫缺陷病毒1型（HIV-1）跨膜包膜糖蛋白gp41介导病毒与细胞融合，在三聚体包膜糖蛋白复合物中至少以三种不同构象存在。融合前状态和中间状态的结构尚不清楚；已解析出代表融合后状态的结构。在融合后构象中，三个螺旋七肽重复序列2（HR2）区域以反平行方式堆积到由七肽重复序列1（HR1）区域形成的三螺旋卷曲螺旋表面的疏水凹槽中。我们通过对HIV-1包膜糖蛋白的膜锚定形式和可溶性形式进行诱变改变，研究了gp41的融合前构象。我们的结果表明，在HIV-1包膜糖蛋白前体中，gp41 HR1区域的构象与三聚体卷曲螺旋的构象不同。因此，中央gp41卷曲螺旋是在HIV-1包膜糖蛋白从前体状态转变为受体结合中间体的过程中形成的。
