A trimeric HIV-1 fusion peptide construct which does not self-associate in aqueous solution and which has 15-fold higher membrane fusion rate |
| |
Authors: | Yang Rong Prorok Mary Castellino Francis J Weliky David P |
| |
Affiliation: | Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|