1i5y
From Proteopedia
(New page: 200px<br /> <applet load="1i5y" size="450" color="white" frame="true" align="right" spinBox="true" caption="1i5y, resolution 2.10Å" /> '''HIV-1 GP41 CORE'''<...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1i5y.gif|left|200px]]<br /> | + | [[Image:1i5y.gif|left|200px]]<br /><applet load="1i5y" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1i5y" size=" | + | |
caption="1i5y, resolution 2.10Å" /> | caption="1i5y, resolution 2.10Å" /> | ||
'''HIV-1 GP41 CORE'''<br /> | '''HIV-1 GP41 CORE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Membrane fusion by human immunodeficiency virus type 1 (HIV-1) is promoted | + | 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== | ==About this Structure== | ||
| - | 1I5Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1I5Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I5Y OCA]. |
==Reference== | ==Reference== | ||
| Line 22: | Line 21: | ||
[[Category: membrane fusion]] | [[Category: membrane fusion]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:08:19 2008'' |
Revision as of 11:08, 21 February 2008
|
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 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 Feb 21 13:08:19 2008
