The influence of cholesterol on the interaction of HIV gp41 membrane proximal region-derived peptides with lipid bilayers.
A small amino acid sequence (LWYIK) inside the HIV-1 gp41 ectodomain membrane proximal region (MPR) is commonly referred to as a cholesterol-binding domain. To further study this unique and peculiar property we have used fluorescence spectroscopy techniques to unravel the membrane interaction properties of three MPR-derived synthetic peptides: the membrane proximal region peptide-complete (MPRP-C) which corresponds to the complete MPR; the membrane proximal region peptide-short (MPRP-S), which corresponds to the last five MPR amino acid residues (the putative cholesterol-binding domain) and the membrane proximal region peptide-intermediate (MPRP-I), which corresponds to the MPRP-C peptide without the MPRP-S sequence. MPRP-C and MPRP-I membrane interaction is largely independent of the membrane phase. Membrane interaction of MPRP-S occurs for fluid phase membranes but not in gel phase membranes or cholesterol-containing bilayers. The gp41 ectodomain MPR may have a very specific function in viral fusion through the concerted and combined action of cholesterol-binding and non-cholesterol-binding domains (i.e. domains corresponding to MPRP-S and MPRP-I, respectively).
Veiga
Ana S
AS
Centro de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Portugal. asveiga@fc.ul.pt
Castanho
Miguel A R B
MA
D002784:Cholesterol / Q000378:metabolism*; D005454:Fluorescence Polarization; D015700:HIV Envelope Protein gp41 / Q000378:metabolism*; D008051:Lipid Bilayers; D011726:Pyridinium Compounds / Q000737:chemistry; D013050:Spectrometry, Fluorescence