Yang Rong, Prorok Mary, Castellino Francis J, Weliky David P
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
J Am Chem Soc. 2004 Nov 17;126(45):14722-3. doi: 10.1021/ja045612o.
A peptide construct (FPtr) was synthesized which mimics the biologically relevant topology of fusion peptide (FP) domains of the trimeric HIV-1 gp41 envelope protein. The FP domains play a critical role in gp41-catalyzed fusion of viral and host cell membranes which is a key step in viral infection. The FPtr construct contains three FP strands chemically bonded at their C-termini through lysine side chains. Analytical ultracentrifugation demonstrated that FPtr does not self-associate in aqueous solution and therefore models the expected FP topology of gp41. Comparative functional fusion assays were carried out using FPtr, FPdm (a cross-linked FP dimer construct), and FPmn (FP monomer). The derived fusion rate constants order ktr > kdm > kmn, and the ratio ktr/kmn has values in the range of 15-40. These results suggest that there is strong correlation of the fusion rate with the biologically relevant trimeric FP topology.
合成了一种肽构建体（FPtr），它模拟了三聚体HIV-1 gp41包膜蛋白融合肽（FP）结构域的生物学相关拓扑结构。FP结构域在gp41催化的病毒膜与宿主细胞膜融合中起关键作用，这是病毒感染的关键步骤。FPtr构建体包含三条通过赖氨酸侧链在其C末端化学键合的FP链。分析超速离心表明，FPtr在水溶液中不会自缔合，因此模拟了gp41预期的FP拓扑结构。使用FPtr、FPdm（一种交联的FP二聚体构建体）和FPmn（FP单体）进行了比较功能融合测定。推导的融合速率常数顺序为ktr > kdm > kmn，ktr/kmn的比值在15-40范围内。这些结果表明，融合速率与生物学相关的三聚体FP拓扑结构之间存在很强的相关性。
