7WWD

Crystal structure of Saccharomyces cerevisiae Sfh2 complexed with squalene


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.39 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Structural basis of ligand recognition and transport by Sfh2, a yeast phosphatidylinositol transfer protein of the Sec14 superfamily.

Chen, L.Tan, L.Im, Y.J.

(2022) Acta Crystallogr D Struct Biol 78: 853-864

  • DOI: https://doi.org/10.1107/S2059798322005666
  • Primary Citation of Related Structures:  
    7WVT, 7WWD, 7WWE, 7WWG

  • 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.


  • Organizational Affiliation

    College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phosphatidylinositol transfer protein CSR1400Saccharomyces cerevisiae S288CMutation(s): 0 
Gene Names: CSR1SFH2YLR380W
UniProt
Find proteins for Q06705 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
Explore Q06705 
Go to UniProtKB:  Q06705
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ06705
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SQL (Subject of Investigation/LOI)
Query on SQL

Download Ideal Coordinates CCD File 
B [auth A](6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
C30 H50
YYGNTYWPHWGJRM-AAJYLUCBSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.39 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.206 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 43.403α = 90
b = 78.278β = 94.113
c = 54.166γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Research Foundation (NRF, Korea)Korea, Republic Of2019R1A2C1085530

Revision History  (Full details and data files)

  • Version 1.0: 2022-07-13
    Type: Initial release
  • Version 1.1: 2024-05-29
    Changes: Data collection