2evt

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[[Image:2evt.gif|left|200px]]<br /><applet load="2evt" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2evt, resolution 1.990&Aring;" />
 
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'''Crystal structure of D48V mutant of human Glycolipid Transfer Protein'''<br />
 
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==Overview==
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==Crystal structure of D48V mutant of human Glycolipid Transfer Protein==
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Lipid transfer proteins are important in membrane vesicle biogenesis and trafficking, signal transduction and immunological presentation processes. The conserved and ubiquitous mammalian glycolipid transfer proteins (GLTPs) serve as potential regulators of cell processes mediated by glycosphingolipids, ranging from differentiation and proliferation to invasive adhesion, neurodegeneration and apoptosis. Here we report crystal structures of apo-GLTP (1.65 A resolution) and lactosylceramide-bound (1.95 A) GLTP, in which the bound glycosphingolipid is sandwiched, after adaptive recognition, within a previously unknown two-layer all-alpha-helical topology. Glycosphingolipid binding specificity is achieved through recognition and anchoring of the sugar-amide headgroup to the GLTP recognition centre by hydrogen bond networks and hydrophobic contacts, and encapsulation of both lipid chains, in a precisely oriented manner within a 'moulded-to-fit' hydrophobic tunnel. A cleft-like conformational gating mechanism, involving two interhelical loops and one alpha-helix of GLTP, could enable the glycolipid chains to enter and leave the tunnel in the membrane-associated state. Mutation and functional analyses of residues in the glycolipid recognition centre and within the hydrophobic tunnel support a framework for understanding how GLTPs acquire and release glycosphingolipids during lipid intermembrane transfer and presentation processes.
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<StructureSection load='2evt' size='340' side='right'caption='[[2evt]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2evt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EVT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2EVT 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]] 1.99&#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=HEX:HEXANE'>HEX</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=2evt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2evt OCA], [https://pdbe.org/2evt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2evt RCSB], [https://www.ebi.ac.uk/pdbsum/2evt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2evt ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GLTP_HUMAN GLTP_HUMAN] Accelerates the intermembrane transfer of various glycolipids. Catalyzes the transfer of various glycosphingolipids between membranes but does not catalyze the transfer of phospholipids. May be involved in the intracellular translocation of glucosylceramides.<ref>PMID:18261224</ref> <ref>PMID:15504043</ref> <ref>PMID:17980653</ref> <ref>PMID:15329726</ref>
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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/ev/2evt_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=2evt 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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Glycosphingolipids (GSLs) play major roles in cellular growth and development. Mammalian glycolipid transfer proteins (GLTPs) are potential regulators of cell processes mediated by GSLs and display a unique architecture among lipid binding/transfer proteins. The GLTP fold represents a novel membrane targeting/interaction domain among peripheral proteins. Here we report crystal structures of human GLTP bound to GSLs of diverse acyl chain length, unsaturation, and sugar composition. Structural comparisons show a highly conserved anchoring of galactosyl- and lactosyl-amide headgroups by the GLTP recognition center. By contrast, acyl chain chemical structure and occupancy of the hydrophobic tunnel dictate partitioning between sphingosine-in and newly-observed sphingosine-out ligand-binding modes. The structural insights, combined with computed interaction propensity distributions, suggest a concerted sequence of events mediated by GLTP conformational changes during GSL transfer to and/or from membranes, as well as during GSL presentation and/or transfer to other proteins.
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==About this Structure==
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The liganding of glycolipid transfer protein is controlled by glycolipid acyl structure.,Malinina L, Malakhova ML, Kanack AT, Lu M, Abagyan R, Brown RE, Patel DJ PLoS Biol. 2006 Nov;4(11):e362. PMID:17105344<ref>PMID:17105344</ref>
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2EVT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=HEX:'>HEX</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EVT 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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Structural basis for glycosphingolipid transfer specificity., Malinina L, Malakhova ML, Teplov A, Brown RE, Patel DJ, Nature. 2004 Aug 26;430(7003):1048-53. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15329726 15329726]
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</div>
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<div class="pdbe-citations 2evt" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Brown, R E.]]
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[[Category: Brown RE]]
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[[Category: Malakhova, M L.]]
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[[Category: Malakhova ML]]
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[[Category: Malinina, L.]]
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[[Category: Malinina L]]
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[[Category: Patel, D J.]]
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[[Category: Patel DJ]]
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[[Category: Teplov, A.]]
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[[Category: Teplov A]]
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[[Category: HEX]]
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[[Category: d48v mutant human gltp]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:15:03 2008''
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Current revision

Crystal structure of D48V mutant of human Glycolipid Transfer Protein

PDB ID 2evt

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