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Cryo-EM structure of human sphingomyelin synthase and its mechanistic implications for sphingomyelin synthesis
by
Li, Shaobai
, Hu, Kexin
, Chen, Yang
, Lu, Hongliang
, Xia, Ying
, Zhou, Lu
, Shen, Yafeng
, Yao, Deqiang
, Jiang, Xian-Cheng
, Cao, Mi
, Cao, Yu
, Yang, Jintong
, Zhang, Qing
, Rao, Bing
, Zhao, Jie
, Qin, An
in
101/28
/ 631/45/287/1194
/ 631/535/1258/1259
/ 631/92/173
/ 82/16
/ 82/29
/ 82/80
/ 82/83
/ Biochemistry
/ Biological Microscopy
/ Biomedical and Life Sciences
/ Biosynthesis
/ Ceramide
/ Ceramides - chemistry
/ Ceramides - metabolism
/ Chambers
/ Chemical synthesis
/ Cryoelectron Microscopy
/ Diglycerides
/ Diglycerides - chemistry
/ Diglycerides - metabolism
/ Ethanolamines - chemistry
/ Ethanolamines - metabolism
/ Helices
/ Homeostasis
/ Humans
/ Life Sciences
/ Lipid metabolism
/ Lipids
/ Lipophilic
/ Membrane Biology
/ Membrane Proteins
/ Models, Molecular
/ Nerve Tissue Proteins - chemistry
/ Nerve Tissue Proteins - metabolism
/ Phosphatidylethanolamine
/ Phosphatidylethanolamines - chemistry
/ Phosphatidylethanolamines - metabolism
/ Phospholipase C
/ Protein Structure
/ Sphingomyelin
/ Sphingomyelins - biosynthesis
/ Sphingomyelins - chemistry
/ Sphingomyelins - metabolism
/ Transferases (Other Substituted Phosphate Groups) - chemistry
/ Transferases (Other Substituted Phosphate Groups) - metabolism
2024
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Cryo-EM structure of human sphingomyelin synthase and its mechanistic implications for sphingomyelin synthesis
by
Li, Shaobai
, Hu, Kexin
, Chen, Yang
, Lu, Hongliang
, Xia, Ying
, Zhou, Lu
, Shen, Yafeng
, Yao, Deqiang
, Jiang, Xian-Cheng
, Cao, Mi
, Cao, Yu
, Yang, Jintong
, Zhang, Qing
, Rao, Bing
, Zhao, Jie
, Qin, An
in
101/28
/ 631/45/287/1194
/ 631/535/1258/1259
/ 631/92/173
/ 82/16
/ 82/29
/ 82/80
/ 82/83
/ Biochemistry
/ Biological Microscopy
/ Biomedical and Life Sciences
/ Biosynthesis
/ Ceramide
/ Ceramides - chemistry
/ Ceramides - metabolism
/ Chambers
/ Chemical synthesis
/ Cryoelectron Microscopy
/ Diglycerides
/ Diglycerides - chemistry
/ Diglycerides - metabolism
/ Ethanolamines - chemistry
/ Ethanolamines - metabolism
/ Helices
/ Homeostasis
/ Humans
/ Life Sciences
/ Lipid metabolism
/ Lipids
/ Lipophilic
/ Membrane Biology
/ Membrane Proteins
/ Models, Molecular
/ Nerve Tissue Proteins - chemistry
/ Nerve Tissue Proteins - metabolism
/ Phosphatidylethanolamine
/ Phosphatidylethanolamines - chemistry
/ Phosphatidylethanolamines - metabolism
/ Phospholipase C
/ Protein Structure
/ Sphingomyelin
/ Sphingomyelins - biosynthesis
/ Sphingomyelins - chemistry
/ Sphingomyelins - metabolism
/ Transferases (Other Substituted Phosphate Groups) - chemistry
/ Transferases (Other Substituted Phosphate Groups) - metabolism
2024
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Cryo-EM structure of human sphingomyelin synthase and its mechanistic implications for sphingomyelin synthesis
by
Li, Shaobai
, Hu, Kexin
, Chen, Yang
, Lu, Hongliang
, Xia, Ying
, Zhou, Lu
, Shen, Yafeng
, Yao, Deqiang
, Jiang, Xian-Cheng
, Cao, Mi
, Cao, Yu
, Yang, Jintong
, Zhang, Qing
, Rao, Bing
, Zhao, Jie
, Qin, An
in
101/28
/ 631/45/287/1194
/ 631/535/1258/1259
/ 631/92/173
/ 82/16
/ 82/29
/ 82/80
/ 82/83
/ Biochemistry
/ Biological Microscopy
/ Biomedical and Life Sciences
/ Biosynthesis
/ Ceramide
/ Ceramides - chemistry
/ Ceramides - metabolism
/ Chambers
/ Chemical synthesis
/ Cryoelectron Microscopy
/ Diglycerides
/ Diglycerides - chemistry
/ Diglycerides - metabolism
/ Ethanolamines - chemistry
/ Ethanolamines - metabolism
/ Helices
/ Homeostasis
/ Humans
/ Life Sciences
/ Lipid metabolism
/ Lipids
/ Lipophilic
/ Membrane Biology
/ Membrane Proteins
/ Models, Molecular
/ Nerve Tissue Proteins - chemistry
/ Nerve Tissue Proteins - metabolism
/ Phosphatidylethanolamine
/ Phosphatidylethanolamines - chemistry
/ Phosphatidylethanolamines - metabolism
/ Phospholipase C
/ Protein Structure
/ Sphingomyelin
/ Sphingomyelins - biosynthesis
/ Sphingomyelins - chemistry
/ Sphingomyelins - metabolism
/ Transferases (Other Substituted Phosphate Groups) - chemistry
/ Transferases (Other Substituted Phosphate Groups) - metabolism
2024
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Cryo-EM structure of human sphingomyelin synthase and its mechanistic implications for sphingomyelin synthesis
Journal Article
Cryo-EM structure of human sphingomyelin synthase and its mechanistic implications for sphingomyelin synthesis
2024
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Overview
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.
Researchers unveiled the structural details of sphingomyelin synthase (SMSr), shedding light on its role in sphingolipid biosynthesis. SMSr transfers the phosphoethanolamine from PE to ceramide, adding complexity to the field of lipid homeostasis.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 82/16
/ 82/29
/ 82/80
/ 82/83
/ Biomedical and Life Sciences
/ Ceramide
/ Chambers
/ Helices
/ Humans
/ Lipids
/ Nerve Tissue Proteins - chemistry
/ Nerve Tissue Proteins - metabolism
/ Phosphatidylethanolamines - chemistry
/ Phosphatidylethanolamines - metabolism
/ Sphingomyelins - biosynthesis
/ Transferases (Other Substituted Phosphate Groups) - chemistry
/ Transferases (Other Substituted Phosphate Groups) - metabolism
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