7wwd

From Proteopedia
Jump to navigation Jump to search

Crystal structure of Saccharomyces cerevisiae Sfh2 complexed with squaleneCrystal structure of Saccharomyces cerevisiae Sfh2 complexed with squalene

Structural highlights

7wwd is a 1 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.39Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).[1] [2] [3] [4] [5] [6] [7] [8]

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[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Santos B, Snyder M. Sbe2p and sbe22p, two homologous Golgi proteins involved in yeast cell wall formation. Mol Biol Cell. 2000 Feb;11(2):435-52. PMID:10679005
  2. ↑ Li X, Routt SM, Xie Z, Cui X, Fang M, Kearns MA, Bard M, Kirsch DR, Bankaitis VA. Identification of a novel family of nonclassic yeast phosphatidylinositol transfer proteins whose function modulates phospholipase D activity and Sec14p-independent cell growth. Mol Biol Cell. 2000 Jun;11(6):1989-2005. PMID:10848624
  3. ↑ Regnacq M, Ferreira T, Puard J, Berges T. SUT1 suppresses sec14-1 through upregulation of CSR1 in Saccharomyces cerevisiae. FEMS Microbiol Lett. 2002 Nov 5;216(2):165-70. doi:, 10.1111/j.1574-6968.2002.tb11431.x. PMID:12435498 doi:http://dx.doi.org/10.1111/j.1574-6968.2002.tb11431.x
  4. ↑ Cha MK, Hong SK, Oh YM, Kim IH. The protein interaction of Saccharomyces cerevisiae cytoplasmic thiol peroxidase II with SFH2p and its in vivo function. J Biol Chem. 2003 Sep 12;278(37):34952-8. doi: 10.1074/jbc.M301819200. Epub 2003 , Jun 24. PMID:12824182 doi:http://dx.doi.org/10.1074/jbc.M301819200
  5. ↑ Schnabl M, Oskolkova OV, Holic R, Brezna B, Pichler H, Zagorsek M, Kohlwein SD, Paltauf F, Daum G, Griac P. Subcellular localization of yeast Sec14 homologues and their involvement in regulation of phospholipid turnover. Eur J Biochem. 2003 Aug;270(15):3133-45. PMID:12869188
  6. ↑ Wong TA, Fairn GD, Poon PP, Shmulevitz M, McMaster CR, Singer RA, Johnston GC. Membrane metabolism mediated by Sec14 family members influences Arf GTPase activating protein activity for transport from the trans-Golgi. Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12777-82. doi:, 10.1073/pnas.0506156102. Epub 2005 Aug 26. PMID:16126894 doi:http://dx.doi.org/10.1073/pnas.0506156102
  7. ↑ Routt SM, Ryan MM, Tyeryar K, Rizzieri KE, Mousley C, Roumanie O, Brennwald PJ, Bankaitis VA. Nonclassical PITPs activate PLD via the Stt4p PtdIns-4-kinase and modulate function of late stages of exocytosis in vegetative yeast. Traffic. 2005 Dec;6(12):1157-72. doi: 10.1111/j.1600-0854.2005.00350.x. PMID:16262726 doi:http://dx.doi.org/10.1111/j.1600-0854.2005.00350.x
  8. ↑ Desfougeres T, Ferreira T, Berges T, Regnacq M. SFH2 regulates fatty acid synthase activity in the yeast Saccharomyces cerevisiae and is critical to prevent saturated fatty acid accumulation in response to haem and oleic acid depletion. Biochem J. 2008 Jan 1;409(1):299-309. doi: 10.1042/BJ20071028. PMID:17803462 doi:http://dx.doi.org/10.1042/BJ20071028
  9. ↑ Chen L, Tan L, Im YJ. Structural basis of ligand recognition and transport by Sfh2, a yeast phosphatidylinositol transfer protein of the Sec14 superfamily. Acta Crystallogr D Struct Biol. 2022 Jul 1;78(Pt 7):853-864. PMID:35775985 doi:10.1107/S2059798322005666

7wwd, resolution 2.39Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=7wwd&oldid=4175579"