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==The cryo-EM structure of human sphingomyelin synthase-related protein in complex with ceramide==
<StructureSection load='8ijq' size='340' side='right'caption='[[8ijq]], [[Resolution|resolution]] 3.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ijq]] is a 6 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=8IJQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IJQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=16C:N-((E,2S,3R)-1,3-DIHYDROXYOCTADEC-4-EN-2-YL)PALMITAMIDE'>16C</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=8ijq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ijq OCA], [https://pdbe.org/8ijq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ijq RCSB], [https://www.ebi.ac.uk/pdbsum/8ijq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ijq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SAMD8_HUMAN SAMD8_HUMAN] Sphingomyelin synthases synthesize sphingolipids through transfer of a phosphatidyl head group on to the primary hydroxyl of ceramide. SAMD8 is an endoplasmic reticulum (ER) transferase that has no sphingomyelin synthase activity but can convert phosphatidylethanolamine (PE) and ceramide to ceramide phosphoethanolamine (CPE) albeit with low product yield. Appears to operate as a ceramide sensor to control ceramide homeostasis in the endoplasmic reticulum rather than a converter of ceramides. Seems to be critical for the integrity of the early secretory pathway.<ref>PMID:19506037</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Sphingomyelin (SM) has key roles in modulating mammalian membrane properties and serves as an important pool for bioactive molecules. SM biosynthesis is mediated by the sphingomyelin synthase (SMS) family, comprising SMS1, SMS2 and SMS-related (SMSr) members. Although SMS1 and SMS2 exhibit SMS activity, SMSr possesses ceramide phosphoethanolamine synthase activity. Here we determined the cryo-electron microscopic structures of human SMSr in complexes with ceramide, diacylglycerol/phosphoethanolamine and ceramide/phosphoethanolamine (CPE). The structures revealed a hexameric arrangement with a reaction chamber located between the transmembrane helices. Within this structure, a catalytic pentad E-H/D-H-D was identified, situated at the interface between the lipophilic and hydrophilic segments of the reaction chamber. Additionally, the study unveiled the two-step synthesis process catalyzed by SMSr, involving PE-PLC (phosphatidylethanolamine-phospholipase C) hydrolysis and the subsequent transfer of the phosphoethanolamine moiety to ceramide. This research provides insights into the catalytic mechanism of SMSr and expands our understanding of sphingolipid metabolism.

Cryo-EM structure of human sphingomyelin synthase and its mechanistic implications for sphingomyelin synthesis.,Hu K, Zhang Q, Chen Y, Yang J, Xia Y, Rao B, Li S, Shen Y, Cao M, Lu H, Qin A, Jiang XC, Yao D, Zhao J, Zhou L, Cao Y Nat Struct Mol Biol. 2024 Jun;31(6):884-895. doi: 10.1038/s41594-024-01237-2. , Epub 2024 Feb 22. PMID:38388831<ref>PMID:38388831</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ijq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cao Y]]
[[Category: Chen Y]]
[[Category: Hu K]]
[[Category: Yao D]]
[[Category: Zhang Q]]
[[Category: Zhou L]]