4hhv: Difference between revisions

Revision as of 08:18, 3 November 2022

Crystal structure of ceramide transfer protein pleckstrin homology domain

Structural highlights

4hhv is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	ACT, CL, GOL, SO4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CERT_HUMAN The disease is caused by variants affecting the gene represented in this entry.

Function

CERT_HUMAN Shelters ceramides and diacylglycerol lipids inside its START domain and mediates the intracellular trafficking of ceramides and diacylglycerol lipids in a non-vesicular manner.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Ceramide transfer protein (CERT) is responsible for the nonvesicular trafficking of ceramide from the endoplasmic reticulum (ER) to the trans Golgi network where it is converted to sphingomyelin (SM). The N-terminal pleckstrin homology (PH) domain is required for Golgi targeting of CERT by recognizing the phosphatidylinositol 4-phosphate (PtdIns(4)P) enriched in the Golgi membrane. We report a crystal structure of the CERT PH domain. This structure contains a sulfate that is hydrogen bonded with residues in the canonical ligand-binding pocket of PH domains. Our nuclear magnetic resonance (NMR) chemical shift perturbation (CSP) analyses show sulfate association with CERT PH protein resembles that of PtdIns(4)P, suggesting that the sulfate bound structure likely mimics the holo form of CERT PH protein. Comparison of the sulfate bound structure with the apo form solution structure shows structural rearrangements likely occur upon ligand binding, suggesting conformational flexibility in the ligand-binding pocket. This structural flexibility likely explains CERT PH domain's low affinity for PtdIns(4)P, a property that is distinct from many other PH domains that bind to their phosphoinositide ligands tightly. This unique structural feature of CERT PH domain is probably tailored towards the transfer activity of CERT protein where it needs to shuttle between ER and Golgi and therefore requires short resident time on ER and Golgi membranes.

Crystal Structure of the Pleckstrin Homology Domain from the Ceramide Transfer Protein: Implications for Conformational Change upon Ligand Binding.,Prashek J, Truong T, Yao X PLoS One. 2013 Nov 18;8(11):e79590. doi: 10.1371/journal.pone.0079590. PMID:24260258^[5]

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

References

↑ Hanada K, Kumagai K, Yasuda S, Miura Y, Kawano M, Fukasawa M, Nishijima M. Molecular machinery for non-vesicular trafficking of ceramide. Nature. 2003 Dec 18;426(6968):803-9. PMID:14685229 doi:https://dx.doi.org/10.1038/nature02188
↑ Fugmann T, Hausser A, Schoffler P, Schmid S, Pfizenmaier K, Olayioye MA. Regulation of secretory transport by protein kinase D-mediated phosphorylation of the ceramide transfer protein. J Cell Biol. 2007 Jul 2;178(1):15-22. Epub 2007 Jun 25. PMID:17591919 doi:https://dx.doi.org/jcb.200612017
↑ Kudo N, Kumagai K, Tomishige N, Yamaji T, Wakatsuki S, Nishijima M, Hanada K, Kato R. Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide. Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):488-93. Epub 2008 Jan 9. PMID:18184806
↑ Kudo N, Kumagai K, Matsubara R, Kobayashi S, Hanada K, Wakatsuki S, Kato R. Crystal structures of the CERT START domain with inhibitors provide insights into the mechanism of ceramide transfer. J Mol Biol. 2010 Feb 19;396(2):245-51. Epub 2009 Dec 28. PMID:20036255 doi:10.1016/j.jmb.2009.12.029
↑ Prashek J, Truong T, Yao X. Crystal Structure of the Pleckstrin Homology Domain from the Ceramide Transfer Protein: Implications for Conformational Change upon Ligand Binding. PLoS One. 2013 Nov 18;8(11):e79590. doi: 10.1371/journal.pone.0079590. PMID:24260258 doi:https://dx.doi.org/10.1371/journal.pone.0079590

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Hanada K, Kumagai K, Yasuda S, Miura Y, Kawano M, Fukasawa M, Nishijima M. Molecular machinery for non-vesicular trafficking of ceramide. Nature. 2003 Dec 18;426(6968):803-9. PMID:14685229 doi:https://dx.doi.org/10.1038/nature02188

[2] Fugmann T, Hausser A, Schoffler P, Schmid S, Pfizenmaier K, Olayioye MA. Regulation of secretory transport by protein kinase D-mediated phosphorylation of the ceramide transfer protein. J Cell Biol. 2007 Jul 2;178(1):15-22. Epub 2007 Jun 25. PMID:17591919 doi:https://dx.doi.org/jcb.200612017

[3] Kudo N, Kumagai K, Tomishige N, Yamaji T, Wakatsuki S, Nishijima M, Hanada K, Kato R. Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide. Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):488-93. Epub 2008 Jan 9. PMID:18184806

[4] Kudo N, Kumagai K, Matsubara R, Kobayashi S, Hanada K, Wakatsuki S, Kato R. Crystal structures of the CERT START domain with inhibitors provide insights into the mechanism of ceramide transfer. J Mol Biol. 2010 Feb 19;396(2):245-51. Epub 2009 Dec 28. PMID:20036255 doi:10.1016/j.jmb.2009.12.029

[5] Prashek J, Truong T, Yao X. Crystal Structure of the Pleckstrin Homology Domain from the Ceramide Transfer Protein: Implications for Conformational Change upon Ligand Binding. PLoS One. 2013 Nov 18;8(11):e79590. doi: 10.1371/journal.pone.0079590. PMID:24260258 doi:https://dx.doi.org/10.1371/journal.pone.0079590

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[2]

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[5]

@@ Line 1: / Line 1: @@
 ==Crystal structure of ceramide transfer protein pleckstrin homology domain==
-<StructureSection load='4hhv' size='340' side='right' caption='[[4hhv]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
+<StructureSection load='4hhv' size='340' side='right'caption='[[4hhv]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4hhv]] is a 2 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=4HHV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HHV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4hhv]] is a 2 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=4HHV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HHV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CERT, COL4A3BP, STARD11 ([http://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'>[https://proteopedia.org/fgij/fg.htm?mol=4hhv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hhv OCA], [https://pdbe.org/4hhv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hhv RCSB], [https://www.ebi.ac.uk/pdbsum/4hhv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hhv ProSAT]</span></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=4hhv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hhv OCA], [http://pdbe.org/4hhv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hhv RCSB], [http://www.ebi.ac.uk/pdbsum/4hhv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hhv ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/CERT_HUMAN CERT_HUMAN] The disease is caused by variants affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/C43BP_HUMAN C43BP_HUMAN]] Shelters ceramides and diacylglycerol lipids inside its START domain and mediates the intracellular trafficking of ceramides and diacylglycerol lipids in a non-vesicular manner.<ref>PMID:14685229</ref> <ref>PMID:17591919</ref> <ref>PMID:18184806</ref> <ref>PMID:20036255</ref>
+[https://www.uniprot.org/uniprot/CERT_HUMAN CERT_HUMAN] Shelters ceramides and diacylglycerol lipids inside its START domain and mediates the intracellular trafficking of ceramides and diacylglycerol lipids in a non-vesicular manner.<ref>PMID:14685229</ref> <ref>PMID:17591919</ref> <ref>PMID:18184806</ref> <ref>PMID:20036255</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Prashek, J]]
+[[Category: Large Structures]]
-[[Category: Truong, T]]
+[[Category: Prashek J]]
-[[Category: Yao, X]]
+[[Category: Truong T]]
-[[Category: Binds to phosphatidylinositol 4-phosphate]]
+[[Category: Yao X]]
-[[Category: Lipid transport]]
-[[Category: Pleckstrin homology domain fold]]

4hhv: Difference between revisions

Revision as of 08:18, 3 November 2022

Crystal structure of ceramide transfer protein pleckstrin homology domain

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

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