EMD-35492
The cryo-EM structure of human sphingomyelin synthase-related protein in complex with ceramide
EMD-35492
Single-particle3.45 Å
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Map released: 28/02/2024
Last modified: 13/11/2024
Sample Organism:
Homo sapiens
Sample: The cryo-EM structure of human sphingomyelin synthase-related protein in complex with ceramide
Fitted models: 8ijq (Avg. Q-score: 0.461)
Deposition Authors: Hu K, Zhang Q, Chen Y, Yao D
,
Zhou L
,
Cao Y
Sample: The cryo-EM structure of human sphingomyelin synthase-related protein in complex with ceramide
Fitted models: 8ijq (Avg. Q-score: 0.461)
Deposition Authors: Hu K, Zhang Q, Chen Y, Yao D
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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
(2024) Nat Struct Mol Biol , 31 , 884 - 895
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(2024) Nat Struct Mol Biol , 31 , 884 - 895
Abstract:
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.
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.