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2c3a

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[[Image:2c3a.gif|left|200px]]<br /><applet load="2c3a" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2c3a, resolution 2.50&Aring;" />
 
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'''STRUCTURE OF UNLIGANDED HSV GD REVEALS A MECHANISM FOR RECEPTOR-MEDIATED ACTIVATION OF VIRUS ENTRY'''<br />
 
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==Overview==
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==Structure of unliganded HSV gD reveals a mechanism for receptor- mediated activation of virus entry==
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Herpes simplex virus (HSV) entry into cells requires binding of the, envelope glycoprotein D (gD) to one of several cell surface receptors. The, 50 C-terminal residues of the gD ectodomain are essential for virus entry, but not for receptor binding. We have determined the structure of an, unliganded gD molecule that includes these C-terminal residues. The, structure reveals that the C-terminus is anchored near the N-terminal, region and masks receptor-binding sites. Locking the C-terminus in the, position observed in the crystals by an intramolecular disulfide bond, abolished receptor binding and virus entry, demonstrating that this region, of gD moves upon receptor binding. Similarly, a point mutant that would, destabilize the C-terminus structure was nonfunctional for entry, despite, increased affinity for receptors. We propose that a controlled, displacement of the gD C-terminus upon receptor binding is an essential, feature of HSV entry, ensuring the timely activation of membrane fusion.
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<StructureSection load='2c3a' size='340' side='right'caption='[[2c3a]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2c3a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_alphaherpesvirus_1 Human alphaherpesvirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C3A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C3A FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2c3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c3a OCA], [https://pdbe.org/2c3a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c3a RCSB], [https://www.ebi.ac.uk/pdbsum/2c3a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c3a ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GD_HHV1P GD_HHV1P] Envelope glycoprotein that binds to the potential host cell entry receptors TNFRSF14/HVEM, PVRL1 and 3-O-sulfated heparan sulfate. May trigger fusion with host membrane, by recruiting the fusion machinery composed of gB and gH/gL (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c3/2c3a_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2c3a ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Herpes simplex virus (HSV) entry into cells requires binding of the envelope glycoprotein D (gD) to one of several cell surface receptors. The 50 C-terminal residues of the gD ectodomain are essential for virus entry, but not for receptor binding. We have determined the structure of an unliganded gD molecule that includes these C-terminal residues. The structure reveals that the C-terminus is anchored near the N-terminal region and masks receptor-binding sites. Locking the C-terminus in the position observed in the crystals by an intramolecular disulfide bond abolished receptor binding and virus entry, demonstrating that this region of gD moves upon receptor binding. Similarly, a point mutant that would destabilize the C-terminus structure was nonfunctional for entry, despite increased affinity for receptors. We propose that a controlled displacement of the gD C-terminus upon receptor binding is an essential feature of HSV entry, ensuring the timely activation of membrane fusion.
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==About this Structure==
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Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry.,Krummenacher C, Supekar VM, Whitbeck JC, Lazear E, Connolly SA, Eisenberg RJ, Cohen GH, Wiley DC, Carfi A EMBO J. 2005 Dec 7;24(23):4144-53. Epub 2005 Nov 17. PMID:16292345<ref>PMID:16292345</ref>
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2C3A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_herpesvirus_4 Human herpesvirus 4] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=NA:'>NA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=AC1:Zn+Binding+Site+For+Chain+B'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C3A OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry., Krummenacher C, Supekar VM, Whitbeck JC, Lazear E, Connolly SA, Eisenberg RJ, Cohen GH, Wiley DC, Carfi A, EMBO J. 2005 Dec 7;24(23):4144-53. Epub 2005 Nov 17. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16292345 16292345]
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</div>
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[[Category: Human herpesvirus 4]]
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<div class="pdbe-citations 2c3a" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Carfi, A.]]
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[[Category: Cohen, G.H.]]
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[[Category: Connolly, S.A.]]
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[[Category: Eisenberg, R.J.]]
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[[Category: Krummenacher, C.]]
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[[Category: Lazear, E.]]
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[[Category: Supekar, V.M.]]
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[[Category: Whitbeck, J.C.]]
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[[Category: Wiley, D.C.]]
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[[Category: CL]]
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[[Category: NA]]
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[[Category: ZN]]
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[[Category: glycoprotein d]]
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[[Category: herpes simplex virus]]
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[[Category: hsv-1]]
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[[Category: viral protein]]
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[[Category: virus]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:30:53 2008''
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==See Also==
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*[[Glycoproteins B and D|Glycoproteins B and D]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Human alphaherpesvirus 1]]
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[[Category: Large Structures]]
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[[Category: Carfi A]]
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[[Category: Cohen GH]]
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[[Category: Connolly SA]]
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[[Category: Eisenberg RJ]]
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[[Category: Krummenacher C]]
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[[Category: Lazear E]]
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[[Category: Supekar VM]]
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[[Category: Whitbeck JC]]
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[[Category: Wiley DC]]

Current revision

Structure of unliganded HSV gD reveals a mechanism for receptor- mediated activation of virus entry

PDB ID 2c3a

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