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A small amino acid sequence (LWYIK) inside the HIV-1 gp41 ectodomain membrane proximal region (MPR) is commonly referred to as a choles-terol-binding domain. To further study this unique and peculiar property we have used fluorescence spectroscopy techniques to unravel the mem-brane interaction properties of three MPR-derived synthetic peptides: the membrane proximal region peptide-complete (MPRP-C) which corresponds to the complete MPR; | ễFEBS Journal The influence of cholesterol on the interaction of HIV gp41 membrane proximal region-derived peptides with lipid bilayers Ana S. Veiga and Miguel A. R. B. Castanho Centro de Quimica e Bioquimica Faculdade de Ciencias da Universidade de Lisboa Portugal Keywords cholesterol gp41 HIV-1 membrane proximalregion membranes Correspondence A. S. Veiga Centro de Quimica e Bioquimica Fac. Ciencias da Universidade Lisboa Campo Grande C8 P 1749-016 Lisbon Portugal Fax 351 21 7500088 Tel 351 21 7500000 E-mail asveiga@fc.ul.pt Received 16 July 2007 revised 1 August 2007 accepted 3 August 2007 doi 10.1111 j.1742-4658.2007.06029.x 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 . HIV-1 entry into target cells occurs through a mechanism mediated by the envelope glycoprotein. Expressed on the surface of the viral membrane as an oligomeric protein trimer this glycoprotein is .
