3rzn: Difference between revisions

Revision as of 10:31, 22 June 2022

Crystal Structure of Human Glycolipid Transfer Protein complexed with 3-O-sulfo-galactosylceramide containing nervonoyl acyl chain (24:1)

Structural highlights

3rzn is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	CIS
Related:	3ric, 3rwv, 2euk, 3s0i, 3s0k
Gene:	GLTP (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Human glycolipid transfer protein (GLTP) fold represents a novel structural motif for lipid binding/transfer and reversible membrane translocation. GLTPs transfer glycosphingolipids (GSLs) that are key regulators of cell growth, division, surface adhesion, and neurodevelopment. Herein, we report structure-guided engineering of the lipid binding features of GLTP. New crystal structures of wild-type GLTP and two mutants (D48V and A47D ||D48V), each containing bound N-nervonoyl-sulfatide, reveal the molecular basis for selective anchoring of sulfatide (3-O-sulfo-galactosylceramide) by D48V-GLTP. Directed point mutations of "portal entrance" residues, A47 and D48, reversibly regulate sphingosine access to the hydrophobic pocket via a mechanism that could involve homodimerization. "Door-opening" conformational changes by phenylalanines within the hydrophobic pocket are revealed during lipid encapsulation by new crystal structures of bona fide apo-GLTP and GLTP complexed with N-oleoyl-glucosylceramide. The development of "engineered GLTPs" with enhanced specificity for select GSLs provides a potential new therapeutic approach for targeting GSL-mediated pathologies.

Enhanced selectivity for sulfatide by engineered human glycolipid transfer protein.,Samygina VR, Popov AN, Cabo-Bilbao A, Ochoa-Lizarralde B, Goni-de-Cerio F, Zhai X, Molotkovsky JG, Patel DJ, Brown RE, Malinina L Structure. 2011 Nov 9;19(11):1644-54. PMID:22078563^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zou X, Chung T, Lin X, Malakhova ML, Pike HM, Brown RE. Human glycolipid transfer protein (GLTP) genes: organization, transcriptional status and evolution. BMC Genomics. 2008 Feb 8;9:72. PMID:18261224 doi:1471-2164-9-72
↑ Rao CS, Lin X, Pike HM, Molotkovsky JG, Brown RE. Glycolipid transfer protein mediated transfer of glycosphingolipids between membranes: a model for action based on kinetic and thermodynamic analyses. Biochemistry. 2004 Nov 2;43(43):13805-15. PMID:15504043 doi:10.1021/bi0492197
↑ Tuuf J, Mattjus P. Human glycolipid transfer protein--intracellular localization and effects on the sphingolipid synthesis. Biochim Biophys Acta. 2007 Nov;1771(11):1353-63. Epub 2007 Sep 21. PMID:17980653 doi:S1388-1981(07)00196-5
↑ Malinina L, Malakhova ML, Teplov A, Brown RE, Patel DJ. Structural basis for glycosphingolipid transfer specificity. Nature. 2004 Aug 26;430(7003):1048-53. PMID:15329726 doi:10.1038/nature02856
↑ Samygina VR, Popov AN, Cabo-Bilbao A, Ochoa-Lizarralde B, Goni-de-Cerio F, Zhai X, Molotkovsky JG, Patel DJ, Brown RE, Malinina L. Enhanced selectivity for sulfatide by engineered human glycolipid transfer protein. Structure. 2011 Nov 9;19(11):1644-54. PMID:22078563 doi:10.1016/j.str.2011.09.011

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Zou X, Chung T, Lin X, Malakhova ML, Pike HM, Brown RE. Human glycolipid transfer protein (GLTP) genes: organization, transcriptional status and evolution. BMC Genomics. 2008 Feb 8;9:72. PMID:18261224 doi:1471-2164-9-72

[2] Rao CS, Lin X, Pike HM, Molotkovsky JG, Brown RE. Glycolipid transfer protein mediated transfer of glycosphingolipids between membranes: a model for action based on kinetic and thermodynamic analyses. Biochemistry. 2004 Nov 2;43(43):13805-15. PMID:15504043 doi:10.1021/bi0492197

[3] Tuuf J, Mattjus P. Human glycolipid transfer protein--intracellular localization and effects on the sphingolipid synthesis. Biochim Biophys Acta. 2007 Nov;1771(11):1353-63. Epub 2007 Sep 21. PMID:17980653 doi:S1388-1981(07)00196-5

[4] Malinina L, Malakhova ML, Teplov A, Brown RE, Patel DJ. Structural basis for glycosphingolipid transfer specificity. Nature. 2004 Aug 26;430(7003):1048-53. PMID:15329726 doi:10.1038/nature02856

[5] Samygina VR, Popov AN, Cabo-Bilbao A, Ochoa-Lizarralde B, Goni-de-Cerio F, Zhai X, Molotkovsky JG, Patel DJ, Brown RE, Malinina L. Enhanced selectivity for sulfatide by engineered human glycolipid transfer protein. Structure. 2011 Nov 9;19(11):1644-54. PMID:22078563 doi:10.1016/j.str.2011.09.011

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Human Glycolipid Transfer Protein complexed with 3-O-sulfo-galactosylceramide containing nervonoyl acyl chain (24:1)==
-<StructureSection load='3rzn' size='340' side='right' caption='[[3rzn]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
+<StructureSection load='3rzn' size='340' side='right'caption='[[3rzn]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3rzn]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RZN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RZN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3rzn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RZN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RZN FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIS:(15Z)-N-((1S,2R,3E)-2-HYDROXY-1-{[(3-O-SULFO-BETA-D-GALACTOPYRANOSYL)OXY]METHYL}HEPTADEC-3-ENYL)TETRACOS-15-ENAMIDE'>CIS</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIS:(15Z)-N-((1S,2R,3E)-2-HYDROXY-1-{[(3-O-SULFO-BETA-D-GALACTOPYRANOSYL)OXY]METHYL}HEPTADEC-3-ENYL)TETRACOS-15-ENAMIDE'>CIS</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ric|3ric]], [[3rwv|3rwv]], [[2euk|2euk]], [[3s0i|3s0i]], [[3s0k|3s0k]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ric|3ric]], [[3rwv|3rwv]], [[2euk|2euk]], [[3s0i|3s0i]], [[3s0k|3s0k]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLTP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLTP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3rzn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rzn OCA], [http://pdbe.org/3rzn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rzn RCSB], [http://www.ebi.ac.uk/pdbsum/3rzn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rzn ProSAT]</span></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=3rzn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rzn OCA], [https://pdbe.org/3rzn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rzn RCSB], [https://www.ebi.ac.uk/pdbsum/3rzn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rzn ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Brown, R E]]
 [[Category: Cabo-Bilbao, A]]

3rzn: Difference between revisions

Revision as of 10:31, 22 June 2022

Crystal Structure of Human Glycolipid Transfer Protein complexed with 3-O-sulfo-galactosylceramide containing nervonoyl acyl chain (24:1)

Structural highlights

Function

Publication Abstract from PubMed

References

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