title: A trimeric HIV-1 fusion peptide construct which does not self-associate in aqueous solution and which has 15-fold higher membrane fusion rate.
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.
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.forename: Mary
authors.initials: M
authors.lastname: Prorok
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Castellino
authors.forename: David P
authors.initials: DP
authors.lastname: Weliky
mesh_terms: D000595:Amino Acid Sequence; D003432:Cross-Linking Reagents / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D005453:Fluorescence; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D007700:Kinetics; D008561:Membrane Fusion / Q000502:physiology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012996:Solutions; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D003432:Cross-Linking Reagents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D012996:Solutions; D014867:Water; D003545:Cysteine