1i5y
From Proteopedia
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HIV-1 GP41 CORE
Overview
Membrane fusion by human immunodeficiency virus type 1 (HIV-1) is promoted, by the refolding of the viral envelope glycoprotein into a fusion-active, conformation. The structure of the gp41 ectodomain core in its, fusion-active state is a trimer of hairpins in which three antiparallel, carboxyl-terminal helices pack into hydrophobic grooves on the surface of, an amino-terminal trimeric coiled coil. In an effort to identify amino, acid residues in these grooves that are critical for gp41 activation, we, have used alanine-scanning mutagenesis to investigate the importance of, individual side chains in determining the biophysical properties of the, gp41 core and the membrane fusion activity of the gp120-gp41 complex., Alanine substitutions at Leu-556, Leu-565, Val-570, Gly-572, and Arg-579, positions severely impaired membrane fusion activity in envelope, glycoproteins that were for the most part normally expressed. Whereas, alanine mutations at Leu-565 and Val-570 destabilized the, trimer-of-hairpins structure, mutations at Gly-572 and Arg-579 led to the, formation of a stable gp41 core. Our results suggest that the Leu-565 and, Val-570 residues are important determinants of conserved packing, interactions between the amino- and carboxyl-terminal helices of gp41. We, propose that the high degree of sequence conservation at Gly-572 and, Arg-579 may result from selective pressures imposed by prefusogenic, conformations of the HIV-1 envelope glycoprotein. Further analysis of the, gp41 activation process may elucidate targets for antiviral intervention.
About this Structure
1I5Y is a Single protein structure of sequence from Human immunodeficiency virus 1 with SO4 as ligand. Full crystallographic information is available from OCA.
Reference
Structural and functional analysis of interhelical interactions in the human immunodeficiency virus type 1 gp41 envelope glycoprotein by alanine-scanning mutagenesis., Lu M, Stoller MO, Wang S, Liu J, Fagan MB, Nunberg JH, J Virol. 2001 Nov;75(22):11146-56. PMID:11602754
Page seeded by OCA on Thu Nov 8 14:09:33 2007
