5YQJ

Crystal structure of the first StARkin domain of Lam4


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.161 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural basis of sterol recognition and nonvesicular transport by lipid transfer proteins anchored at membrane contact sites

Tong, J.Manik, M.K.Im, Y.J.

(2018) Proc Natl Acad Sci U S A 115: E856-E865

  • DOI: https://doi.org/10.1073/pnas.1719709115
  • Primary Citation of Related Structures:  
    5YQI, 5YQJ, 5YQP, 5YQQ, 5YQR, 5YS0

  • PubMed Abstract: 

    Membrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid exchange, which is essential for many biological functions, including regulation of membrane properties and protein trafficking. Lipid transfer proteins anchored at membrane contact sites (LAMs) contain sterol-specific lipid transfer domains [StARkin domain (SD)] and multiple targeting modules to specific membrane organelles. Elucidating the structural mechanisms of targeting and ligand recognition by LAMs is important for understanding the interorganelle communication and exchange at MCSs. Here, we determined the crystal structures of the yeast Lam6 pleckstrin homology (PH)-like domain and the SDs of Lam2 and Lam4 in the apo form and in complex with ergosterol. The Lam6 PH-like domain displays a unique PH domain fold with a conserved N-terminal α-helix. The Lam6 PH-like domain lacks the basic surface for phosphoinositide binding, but contains hydrophobic patches on its surface, which are critical for targeting to endoplasmic reticulum (ER)-mitochondrial contacts. Structures of the LAM SDs display a helix-grip fold with a hydrophobic cavity and a flexible Ω1-loop as a lid. Ergosterol is bound to the pocket in a head-down orientation, with its hydrophobic acyl group located in the tunnel entrance. The Ω1-loop in an open conformation is essential for ergosterol binding by direct hydrophobic interaction. Structural comparison suggested that the sterol binding mode of the Lam2 SD2 is likely conserved among the sterol transfer proteins of the StARkin superfamily. Structural models of full-length Lam2 correlated with the sterol transport function at the membrane contact sites.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Membrane-anchored lipid-binding protein LAM4
A, B, C
187Saccharomyces cerevisiae S288CMutation(s): 0 
Gene Names: LAM4LTC3YHR080C
Membrane Entity: Yes 
UniProt
Find proteins for P38800 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
Explore P38800 
Go to UniProtKB:  P38800
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP38800
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.161 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 38.813α = 90
b = 54.95β = 95.08
c = 119.478γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Korea, Republic Of--

Revision History  (Full details and data files)

  • Version 1.0: 2018-01-31
    Type: Initial release
  • Version 1.1: 2018-02-14
    Changes: Database references
  • Version 1.2: 2024-03-27
    Changes: Data collection, Database references