3H3S

Crystal structure of the CERT START domain in complex with HPA-15

3H3S の概要

• エントリーDOI: 10.2210/pdb3h3s/pdb
• 関連するPDBエントリー: 2E3M 2E3N 2E3O 2E3P 2E3Q 2E3R 2E3S 3H3Q 3H3R 3H3T
• 分子名称: Goodpasture antigen binding protein, N-[(1R,3R)-3-hydroxy-1-(hydroxymethyl)-3-phenylpropyl]pentadecanamide (3 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: 2
• 化学式量合計: 58674.76

構造登録者

Kudo, N.,Wakatsuki, S.,Kato, R. (登録日: 2009-04-17, 公開日: 2010-03-02, 最終更新日: 2024-03-20)

主引用文献

Kudo, N.,Kumagai, K.,Matsubara, R.,Kobayashi, S.,Hanada, K.,Wakatsuki, S.,Kato, R.
Crystal structures of the CERT START domain with inhibitors provide insights into the mechanism of ceramide transfer.
J.Mol.Biol., 396:245-251, 2010

PubMed Abstract: The cytosolic protein CERT transfers ceramide from the endoplasmic reticulum to the Golgi apparatus where ceramide is converted to SM. The C-terminal START (steroidogenic acute regulatory protein-related lipid transfer) domain of CERT binds one ceramide molecule in its central amphiphilic cavity. (1R,3R)-N-(3-Hydroxy-1-hydroxymethyl-3-phenylpropyl)alkanamide (HPA), a synthesized analogue of ceramide, inhibits ceramide transfer by CERT. Here we report crystal structures of the CERT START domain in complex with HPAs of varying acyl chain lengths. In these structures, one HPA molecule is buried in the amphiphilic cavity where the amide and hydroxyl groups of HPA form a hydrogen-bond network with specific amino acid residues. The Omega1 loop, which has been suggested to function as a gate of the cavity, adopts a different conformation when bound to HPA than when bound to ceramide. In the Omega1 loop region, Trp473 shows the largest difference between these two structures. This residue exists inside of the cavity in HPA-bound structures, while it is exposed to the outside of the protein in the apo-form and ceramide-bound complex structures. Surface plasmon resonance experiments confirmed that Trp473 is important for interaction with membranes. These results provide insights into not only the molecular mechanism of inhibition by HPAs but also possible mechanisms by which CERT interacts with ceramide.

PubMed: 20036255
DOI: 10.1016/j.jmb.2009.12.029

実験手法

X-RAY DIFFRACTION (1.66 Å)