8IJR

The cryo-EM structure of human sphingomyelin synthase-related protein in complex with diacylglycerol/phosphoethanolamine

8IJR の概要

• エントリーDOI: 10.2210/pdb8ijr/pdb
• EMDBエントリー: 35493
• 分子名称: Sphingomyelin synthase-related protein 1, (2S)-1-(hexadecanoyloxy)-3-hydroxypropan-2-yl (11Z)-octadec-11-enoate, PHOSPHORIC ACID MONO-(2-AMINO-ETHYL) ESTER (3 entities in total)
• 機能のキーワード: synthase, sphingomyelin, cpe, membrane protein, lipid metabolism
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 294092.66

構造登録者

Hu, K.,Zhang, Q.,Chen, Y.,Yao, D.,Zhou, L.,Cao, Y. (登録日: 2023-02-28, 公開日: 2024-02-28, 最終更新日: 2024-07-03)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.29 Å)