1i5y: Difference between revisions

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-[[Image:1i5y.gif|left|200px]]<br />
-<applet load="1i5y" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1i5y, resolution 2.10&Aring;" />
-'''HIV-1 GP41 CORE'''<br />
-==Overview==
+==HIV-1 GP41 CORE==
-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.
+<StructureSection load='1i5y' size='340' side='right'caption='[[1i5y]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1i5y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I5Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I5Y FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1i5y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i5y OCA], [https://pdbe.org/1i5y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i5y RCSB], [https://www.ebi.ac.uk/pdbsum/1i5y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i5y ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q76270_9HIV1 Q76270_9HIV1]
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i5/1i5y_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1i5y ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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==
+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<ref>PMID:11602754</ref>
-I5Y 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1I5Y OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11602754 11602754]
+</div>
+<div class="pdbe-citations 1i5y" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Gp41 3D Structures|Gp41 3D Structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Human immunodeficiency virus 1]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Liu, J.]]
+[[Category: Liu J]]
-[[Category: Lu, M.]]
+[[Category: Lu M]]
-[[Category: SO4]]
-[[Category: gp41]]
-[[Category: hiv-1]]
-[[Category: hiv-1 inhibition]]
-[[Category: membrane fusion]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov  8 14:09:33 2007''