7WWD

Crystal structure of Saccharomyces cerevisiae Sfh2 complexed with squalene

7WWD の概要

• エントリーDOI: 10.2210/pdb7wwd/pdb
• 分子名称: Phosphatidylinositol transfer protein CSR1, (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene (3 entities in total)
• 機能のキーワード: sec14, phosphatidylinositol, squalene, transport, lipid transport
• 由来する生物種: Saccharomyces cerevisiae S288C
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46981.36

構造登録者

Chen, L.,Tan, L.,Im, Y.J. (登録日: 2022-02-12, 公開日: 2022-07-13, 最終更新日: 2024-05-29)

主引用文献

Chen, L.,Tan, L.,Im, Y.J.
Structural basis of ligand recognition and transport by Sfh2, a yeast phosphatidylinositol transfer protein of the Sec14 superfamily.
Acta Crystallogr D Struct Biol, 78:853-864, 2022

PubMed Abstract: Sec14-like phosphatidylinositol transfer proteins (PITPs) are involved in lipid metabolism and phosphatidylinositol 4-phosphate signaling by transporting phosphatidylinositol (PI) and a secondary ligand between the organellar membranes in eukaryotes. Yeast Sfh2 is a PITP that transfers PI and squalene without phosphatidylcholine transfer activity. To investigate the structural determinants for ligand specificity and transport in Sfh2, crystal structures of Sfh2 in complex with PI and squalene were determined at 1.5 and 2.4 Å resolution, respectively. The inositol head group of PI is recognized by highly conserved residues around the pocket entrance. The acyl chains of PI bind into a large hydrophobic cavity. Squalene is accommodated in the bottom of the cavity entirely by hydrophobic interactions. The binding of PI and squalene are mutually exclusive due to their overlapping binding sites, correlating with the role in lipid exchange. The binding mode of PI is well conserved in Sfh family proteins. However, squalene binding is unique to the Sfh2 homolog due to the specific hydrophobic residues forming a shape-complementary binding pocket. Recombinant apo Sfh2 forms a homodimer in vitro by the hydrophobic interaction of the gating α10-α11 helices in an open conformation. Ligand binding closes the lid and dissociates the dimer into monomers. This study reveals the structural determinants for the recognition of the conserved PI and a secondary ligand, squalene, and provides implications for the lipid-transfer function of Sfh2.

PubMed: 35775985
DOI: 10.1107/S2059798322005666

実験手法

X-RAY DIFFRACTION (2.39 Å)