8ijq | pdb_00008ijq

The cryo-EM structure of human sphingomyelin synthase-related protein in complex with ceramide

spinqualitylabelsall models 8ijq, resolution 3.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ijq is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.45Å Ligands: 16C Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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