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==Crystal structure of Saccharomyces cerevisiae Sfh2 complexed with squalene==
<StructureSection load='7wwd' size='340' side='right'caption='[[7wwd]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7wwd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WWD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WWD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.39&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SQL:(6E,10E,14E,18E)-2,6,10,15,19,23-HEXAMETHYLTETRACOSA-2,6,10,14,18,22-HEXAENE'>SQL</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7wwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wwd OCA], [https://pdbe.org/7wwd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wwd RCSB], [https://www.ebi.ac.uk/pdbsum/7wwd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wwd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CSR1_YEAST CSR1_YEAST] Non-classical phosphatidylinositol (PtdIns) transfer protein (PITP), which exhibits PtdIns-binding/transfer activity in the absence of detectable PtdCho-binding/transfer activity. Activates SPO14/PLD1 (phospholipase D1) by stimulating phosphoinositide synthesis via the STT4 PtdIns 4-kinase. Modulates ArfGAP function through effects on SPO14 activity. Inhibits phosphatidylcholine degradation by PLB1 (phospholipase B1). May also regulate post-Golgi membrane-trafficking events and have a role resistance to oxidative stress. Inhibits fatty acid synthase activity in response to heme depletion and oleic acid starvation, preventing saturated fatty acid (SFA) accumulation (PubMed:17803462).<ref>PMID:10679005</ref> <ref>PMID:10848624</ref> <ref>PMID:12435498</ref> <ref>PMID:12824182</ref> <ref>PMID:12869188</ref> <ref>PMID:16126894</ref> <ref>PMID:16262726</ref> <ref>PMID:17803462</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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 A 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 alpha10-alpha11 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.

Structural basis of ligand recognition and transport by Sfh2, a yeast phosphatidylinositol transfer protein of the Sec14 superfamily.,Chen L, Tan L, Im YJ Acta Crystallogr D Struct Biol. 2022 Jul 1;78(Pt 7):853-864. doi: , 10.1107/S2059798322005666. Epub 2022 Jun 14. PMID:35775985<ref>PMID:35775985</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7wwd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Chen L]]
[[Category: Im YJ]]
[[Category: Tan L]]