8W9Y

The cryo-EM structure of human sphingomyelin synthase-related protein

Summary for 8W9Y

• Entry DOI: 10.2210/pdb8w9y/pdb
• EMDB information: 37385
• Descriptor: Sphingomyelin synthase-related protein 1 (1 entity in total)
• Functional Keywords: synthase, sphingomyelin, cpe, membrane protein, lipid metabolism
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 6
• Total formula weight: 186339.17

Authors

Hu, K.,Zhang, Q.,Chen, Y.,Yao, D.,Zhou, L.,Cao, Y. (deposition date: 2023-09-06, release date: 2024-02-28, Last modification date: 2024-11-13)

Primary citation

Hu, K.,Zhang, Q.,Chen, Y.,Yang, J.,Xia, Y.,Rao, B.,Li, S.,Shen, Y.,Cao, M.,Lu, H.,Qin, A.,Jiang, X.C.,Yao, D.,Zhao, J.,Zhou, L.,Cao, Y.
Cryo-EM structure of human sphingomyelin synthase and its mechanistic implications for sphingomyelin synthesis.
Nat.Struct.Mol.Biol., 31:884-895, 2024

PubMed 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.

PubMed: 38388831
DOI: 10.1038/s41594-024-01237-2

Experimental method

ELECTRON MICROSCOPY (3.5 Å)