Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
J Am Chem Soc. 2011 Jul 6;133(26):10038-41. doi: 10.1021/ja203358t. Epub 2011 Jun 14.
Infection of cells by HIV depends upon profound structural rearrangements within the trimeric viral protein gp41. Critical to this process is the formation of a six-helix bundle in which a set of three N-terminal heptad repeat (NHR) helices assemble to form a core displaying long grooves that provide docking sites for three C-terminal heptad repeat (CHR) helices. We report experiments designed to discriminate between two alternative hypotheses regarding the source of affinity between individual CHR helices and the complementary groove: (1) affinity is dominated by interactions of a small cluster of side chains at one end of the CHR helix; or (2) affinity depends upon interactions distributed across the long CHR helix. We have employed two complementary experimental designs, and results from both favor the latter hypothesis.
HIV 感染细胞依赖于三聚体病毒蛋白 gp41 内深刻的结构重排。这一过程的关键是形成一个六螺旋束，其中一组三个 N 端七肽重复（NHR）螺旋组装形成一个核心，显示出长槽，为三个 C 端七肽重复（CHR）螺旋提供对接位点。我们报告了旨在区分关于单个 CHR 螺旋与互补凹槽之间亲和力来源的两种替代假设的实验：（1）亲和力主要由 CHR 螺旋一端的一小簇侧链相互作用决定；或（2）亲和力取决于 CHR 螺旋上分布的相互作用。我们采用了两种互补的实验设计，结果都支持后一种假设。
