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==crystal structure of the ceramide transfer protein PH and START domain complex==
<StructureSection load='5jjd' size='340' side='right'caption='[[5jjd]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5jjd]] 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=5JJD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JJD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.403&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></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=5jjd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jjd OCA], [https://pdbe.org/5jjd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jjd RCSB], [https://www.ebi.ac.uk/pdbsum/5jjd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jjd 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 ==
[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 ==
De novo synthesis of the sphingolipid sphingomyelin requires non-vesicular transport of ceramide from the endoplasmic reticulum to the Golgi by the multidomain protein ceramide transfer protein (CERT). CERT's N-terminal pleckstrin homology (PH) domain targets it to the Golgi by binding to phosphatidylinositol 4-phosphate (PtdIns(4)P) in the Golgi membrane, whereas its C-terminal StAR-related lipid transfer domain (START) carries out ceramide transfer. Hyperphosphorylation of a serine-rich motif immediately after the PH domain decreases both PtdIns(4)P binding and ceramide transfer by CERT. This down-regulation requires both the PH and START domains, suggesting a possible inhibitory interaction between the two domains. In this study we show that isolated PH and START domains interact with each other. The crystal structure of a PH-START complex revealed that the START domain binds to the PH domain at the same site for PtdIns(4)P-binding, suggesting that the START domain competes with PtdIns(4)P for association with the PH domain. We further report that mutations disrupting the PH-START interaction increase both PtdIns(4)P-binding affinity and ceramide transfer activity of a CERT-serine-rich phosphorylation mimic. We also found that these mutations increase the Golgi localization of CERT inside the cell, consistent with enhanced PtdIns(4)P binding of the mutant. Collectively, our structural, biochemical, and cellular investigations provide important structural insight into the regulation of CERT function and localization.

Interaction between the PH and START domains of ceramide transfer protein competes with phosphatidylinositol 4-phosphate binding by the PH domain.,Prashek J, Bouyain S, Fu M, Li Y, Berkes D, Yao X J Biol Chem. 2017 Aug 25;292(34):14217-14228. doi: 10.1074/jbc.M117.780007. Epub , 2017 Jun 26. PMID:28652409<ref>PMID:28652409</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5jjd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bouyain S]]
[[Category: Prashek J]]
[[Category: Yao X]]