2E3O

Crystal structure of CERT START domain in complex with C16-ceramide (P212121)

2E3O の概要

• エントリーDOI: 10.2210/pdb2e3o/pdb
• 関連するPDBエントリー: 2E3M 2E3N 2E3P 2E3Q 2E3R 2E3S
• 分子名称: Lipid-transfer protein CERT, N-((E,2S,3R)-1,3-DIHYDROXYOCTADEC-4-EN-2-YL)PALMITAMIDE, DIMETHYL SULFOXIDE, ... (4 entities in total)
• 機能のキーワード: lipid transfer protein, cert, ceramide transfer, lipid transport
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29625.93

構造登録者

Kudo, N.,Kumagai, K.,Wakatsuki, S.,Nishijima, M.,Hanada, K.,Kato, R. (登録日: 2006-11-28, 公開日: 2007-12-18, 最終更新日: 2024-03-13)

主引用文献

Kudo, N.,Kumagai, K.,Tomishige, N.,Yamaji, T.,Wakatsuki, S.,Nishijima, M.,Hanada, K.,Kato, R.
Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide.
Proc.Natl.Acad.Sci.Usa, 105:488-493, 2008

PubMed Abstract: In mammalian cells, ceramide is synthesized in the endoplasmic reticulum and transferred to the Golgi apparatus for conversion to sphingomyelin. Ceramide transport occurs in a nonvesicular manner and is mediated by CERT, a cytosolic 68-kDa protein with a C-terminal steroidogenic acute regulatory protein-related lipid transfer (START) domain. The CERT START domain efficiently transfers natural D-erythro-C16-ceramide, but not lipids with longer (C20) amide-acyl chains. The molecular mechanisms of ceramide specificity, both stereo-specific recognition and length limit, are not well understood. Here we report the crystal structures of the CERT START domain in its apo-form and in complex with ceramides having different acyl chain lengths. In these complex structures, one ceramide molecule is buried in a long amphiphilic cavity. At the far end of the cavity, the amide and hydroxyl groups of ceramide form a hydrogen bond network with specific amino acid residues that play key roles in stereo-specific ceramide recognition. At the head of the ceramide molecule, there is no extra space to accommodate additional bulky groups. The two aliphatic chains of ceramide are surrounded by the hydrophobic wall of the cavity, whose size and shape dictate the length limit for cognate ceramides. Furthermore, local high-crystallographic B-factors suggest that the alpha-3 and the Omega1 loop might work as a gate to incorporate the ceramide into the cavity. Thus, the structures demonstrate the structural basis for the mechanism by which CERT can distinguish ceramide from other lipid types yet still recognize multiple species of ceramides.

PubMed: 18184806
DOI: 10.1073/pnas.0709191105

実験手法

X-RAY DIFFRACTION (1.55 Å)