7WWD

Crystal structure of Saccharomyces cerevisiae Sfh2 complexed with squalene

Summary for 7WWD

• Entry DOI: 10.2210/pdb7wwd/pdb
• Descriptor: 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)
• Functional Keywords: sec14, phosphatidylinositol, squalene, transport, lipid transport
• Biological source: Saccharomyces cerevisiae S288C
• Total number of polymer chains: 1
• Total formula weight: 46981.36

Authors

Chen, L.,Tan, L.,Im, Y.J. (deposition date: 2022-02-12, release date: 2022-07-13, Last modification date: 2024-05-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.39 Å)