1I5X

HIV-1 GP41 CORE

Summary for 1I5X

• Entry DOI: 10.2210/pdb1i5x/pdb
• Related: 1I5Y
• Descriptor: TRANSMEMBRANE GLYCOPROTEIN (GP41), SULFATE ION (3 entities in total)
• Functional Keywords: gp41, hiv-1, membrane fusion, hiv-1 inhibition, viral protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 1
• Total formula weight: 7889.70

Authors

Liu, J.,Lu, M. (deposition date: 2001-03-01, release date: 2002-09-10, Last modification date: 2023-08-09)

Primary citation

Lu, M.,Stoller, M.O.,Wang, S.,Liu, J.,Fagan, M.B.,Nunberg, J.H.
Structural and functional analysis of interhelical interactions in the human immunodeficiency virus type 1 gp41 envelope glycoprotein by alanine-scanning mutagenesis.
J.Virol., 75:11146-11156, 2001

PubMed Abstract: 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.

PubMed: 11602754
DOI: 10.1128/JVI.75.22.11146-11156.2001

Experimental method

X-RAY DIFFRACTION (1.8 Å)