1ZI7

Structure of truncated yeast oxysterol binding protein Osh4

1ZI7 の概要

• エントリーDOI: 10.2210/pdb1zi7/pdb
• 関連するPDBエントリー: 1zht 1zhw 1zhx 1zhy 1zhz
• 分子名称: KES1 protein, SULFATE ION (3 entities in total)
• 機能のキーワード: oxysterol, sterol binding protein, lipid binding protein
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 140051.08

構造登録者

Im, Y.J.,Raychaudhuri, S.,Prinz, W.A.,Hurley, J.H. (登録日: 2005-04-27, 公開日: 2005-09-06, 最終更新日: 2023-08-23)

主引用文献

Im, Y.J.,Raychaudhuri, S.,Prinz, W.A.,Hurley, J.H.
Structural mechanism for sterol sensing and transport by OSBP-related proteins
Nature, 437:154-158, 2005

PubMed Abstract: The oxysterol-binding-protein (OSBP)-related proteins (ORPs) are conserved from yeast to humans, and are implicated in the regulation of sterol homeostasis and in signal transduction pathways. Here we report the structure of the full-length yeast ORP Osh4 (also known as Kes1) at 1.5-1.9 A resolution in complexes with ergosterol, cholesterol, and 7-, 20- and 25-hydroxycholesterol. We find that a single sterol molecule binds within a hydrophobic tunnel in a manner consistent with a transport function for ORPs. The entrance is blocked by a flexible amino-terminal lid and surrounded by basic residues that are critical for Osh4 function. The structure of the open state of a lid-truncated form of Osh4 was determined at 2.5 A resolution. Structural analysis and limited proteolysis show that sterol binding closes the lid and stabilizes a conformation favouring transport across aqueous barriers and signal transmission. The structure of Osh4 in the absence of ligand exposes potential phospholipid-binding sites that are positioned for membrane docking and sterol exchange. On the basis of these observations, we propose a model in which sterol and membrane binding promote reciprocal conformational changes that facilitate a sterol transfer and signalling cycle.

PubMed: 16136145
DOI: 10.1038/nature03923

実験手法

X-RAY DIFFRACTION (2.5 Å)