2lcy
From Proteopedia
(Difference between revisions)
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<StructureSection load='2lcy' size='340' side='right' caption='[[2lcy]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | <StructureSection load='2lcy' size='340' side='right' caption='[[2lcy]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | [[2lcy]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Zaire_ebolavirus Zaire ebolavirus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LCY OCA]. <br> | + | <table><tr><td colspan='2'>[[2lcy]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Zaire_ebolavirus Zaire ebolavirus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LCY OCA]. <br> |
| - | <b>[[Related_structure|Related:]]</b> [[2lcz|2lcz]]< | + | </td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2lcz|2lcz]]</td></tr> |
| - | <b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span>< | + | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=186538 Zaire ebolavirus])</td></tr> |
| - | <b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2lcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lcy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lcy RCSB], [http://www.ebi.ac.uk/pdbsum/2lcy PDBsum]</span>< | + | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr> |
| + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2lcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lcy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lcy RCSB], [http://www.ebi.ac.uk/pdbsum/2lcy PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Ebolavirus (Ebov), an enveloped virus of the family Filoviridae, causes hemorrhagic fever in humans and nonhuman primates. The viral glycoprotein (GP) is solely responsible for virus-host membrane fusion, but how it does so remains elusive. Fusion occurs after virions reach an endosomal compartment where GP is proteolytically primed by cathepsins. Fusion by primed GP is governed by an internal fusion loop found in GP2, the fusion subunit. This fusion loop contains a stretch of hydrophobic residues, some of which have been shown to be critical for GP-mediated infection. Here we present liposome fusion data and NMR structures for a complete (54-residue) disulfide-bonded internal fusion loop (Ebov FL) in a membrane mimetic. The Ebov FL induced rapid fusion of liposomes of varying compositions at pH values at or below 5.5. Consistently, circular dichroism experiments indicated that the alpha-helical content of the Ebov FL in the presence of either lipid-mimetic micelles or small liposomes increases in samples exposed to pH </=5.5. NMR structures in dodecylphosphocholine micelles at pH 7.0 and 5.5 revealed a conformational change from a relatively flat extended loop structure at pH 7.0 to a structure with an approximately 90 degrees bend at pH 5.5. Induction of the bend at low pH reorients and compacts the hydrophobic patch at the tip of the FL. We propose that these changes facilitate disruption of lipids at the site of virus-host cell membrane contact and, hence, initiate Ebov fusion. | Ebolavirus (Ebov), an enveloped virus of the family Filoviridae, causes hemorrhagic fever in humans and nonhuman primates. The viral glycoprotein (GP) is solely responsible for virus-host membrane fusion, but how it does so remains elusive. Fusion occurs after virions reach an endosomal compartment where GP is proteolytically primed by cathepsins. Fusion by primed GP is governed by an internal fusion loop found in GP2, the fusion subunit. This fusion loop contains a stretch of hydrophobic residues, some of which have been shown to be critical for GP-mediated infection. Here we present liposome fusion data and NMR structures for a complete (54-residue) disulfide-bonded internal fusion loop (Ebov FL) in a membrane mimetic. The Ebov FL induced rapid fusion of liposomes of varying compositions at pH values at or below 5.5. Consistently, circular dichroism experiments indicated that the alpha-helical content of the Ebov FL in the presence of either lipid-mimetic micelles or small liposomes increases in samples exposed to pH </=5.5. NMR structures in dodecylphosphocholine micelles at pH 7.0 and 5.5 revealed a conformational change from a relatively flat extended loop structure at pH 7.0 to a structure with an approximately 90 degrees bend at pH 5.5. Induction of the bend at low pH reorients and compacts the hydrophobic patch at the tip of the FL. We propose that these changes facilitate disruption of lipids at the site of virus-host cell membrane contact and, hence, initiate Ebov fusion. | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 09:48, 1 May 2014
NMR Structure of the Complete Internal Fusion Loop from Ebolavirus GP2 at pH 5.5
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