4OMJ

Crystal structure of SPF bound to 2,3-oxidosqualene

4OMJ の概要

• エントリーDOI: 10.2210/pdb4omj/pdb
• 関連するPDBエントリー: 1O6U 1OLM 4OMK
• 分子名称: SEC14-like protein 2, SULFATE ION, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: cholesterol synthesis, squalene, 2, 3-oxidosqualene, sec14-like, cral-trio domain, hydrophobic ligand transporter, transport protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: O76054
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65823.12

構造登録者

Christen, M.,Marcaida, M.J.,Lamprakis, C.,Cascella, M.,Stocker, A. (登録日: 2014-01-27, 公開日: 2015-04-15, 最終更新日: 2023-09-20)

主引用文献

Christen, M.,Marcaida, M.J.,Lamprakis, C.,Aeschimann, W.,Vaithilingam, J.,Schneider, P.,Hilbert, M.,Schneider, G.,Cascella, M.,Stocker, A.
Structural insights on cholesterol endosynthesis: Binding of squalene and 2,3-oxidosqualene to supernatant protein factor.
J.Struct.Biol., 190:261-270, 2015

PubMed Abstract: We present the crystal structures of the SEC14-like domain of supernatant protein factor (SPF) in complex with squalene and 2,3-oxidosqualene. The structures were resolved at 1.75Å (complex with squalene) and 1.6Å resolution (complex with 2,3-oxidosqualene), leading in both cases to clear images of the protein/substrate interactions. Ligand binding is facilitated by removal of the Golgi-dynamics (GOLD) C-terminal domain of SPF, which, as shown in previous structures of the apo-protein, blocked the opening of the binding pocket to the exterior. Both substrates bind into a large hydrophobic cavity, typical of such lipid-transporter family. Our structures report no specific recognition mode for the epoxide group. In fact, for both molecules, ligand affinity is dominated by hydrophobic interactions, and independent investigations by computational models or differential scanning micro-calorimetry reveal similar binding affinities for both ligands. Our findings elucidate the molecular bases of the role of SPF in sterol endo-synthesis, supporting the original hypothesis that SPF is a facilitator of substrate flow within the sterol synthetic pathway. Moreover, our results suggest that the GOLD domain acts as a regulator, as its conformational displacement must occur to favor ligand binding and release during the different synthetic steps.

PubMed: 25987292
DOI: 10.1016/j.jsb.2015.05.001

実験手法

X-RAY DIFFRACTION (1.6 Å)