2E3P

Crystal structure of CERT START domain in complex with C16-cearmide (P1)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.219 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide.

Kudo, N.Kumagai, K.Tomishige, N.Yamaji, T.Wakatsuki, S.Nishijima, M.Hanada, K.Kato, R.

(2008) Proc Natl Acad Sci U S A 105: 488-493

  • DOI: https://doi.org/10.1073/pnas.0709191105
  • Primary Citation of Related Structures:  
    2E3M, 2E3N, 2E3O, 2E3P, 2E3Q, 2E3R, 2E3S, 2Z9Y, 2Z9Z

  • PubMed Abstract: 

    In mammalian cells, ceramide is synthesized in the endoplasmic reticulum and transferred to the Golgi apparatus for conversion to sphingomyelin. Ceramide transport occurs in a nonvesicular manner and is mediated by CERT, a cytosolic 68-kDa protein with a C-terminal steroidogenic acute regulatory protein-related lipid transfer (START) domain. The CERT START domain efficiently transfers natural D-erythro-C16-ceramide, but not lipids with longer (C20) amide-acyl chains. The molecular mechanisms of ceramide specificity, both stereo-specific recognition and length limit, are not well understood. Here we report the crystal structures of the CERT START domain in its apo-form and in complex with ceramides having different acyl chain lengths. In these complex structures, one ceramide molecule is buried in a long amphiphilic cavity. At the far end of the cavity, the amide and hydroxyl groups of ceramide form a hydrogen bond network with specific amino acid residues that play key roles in stereo-specific ceramide recognition. At the head of the ceramide molecule, there is no extra space to accommodate additional bulky groups. The two aliphatic chains of ceramide are surrounded by the hydrophobic wall of the cavity, whose size and shape dictate the length limit for cognate ceramides. Furthermore, local high-crystallographic B-factors suggest that the alpha-3 and the Omega1 loop might work as a gate to incorporate the ceramide into the cavity. Thus, the structures demonstrate the structural basis for the mechanism by which CERT can distinguish ceramide from other lipid types yet still recognize multiple species of ceramides.


  • Organizational Affiliation

    Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki 305-0801, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Lipid-transfer protein CERT
A, B
255Homo sapiensMutation(s): 0 
Gene Names: CERT
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y5P4 (Homo sapiens)
Explore Q9Y5P4 
Go to UniProtKB:  Q9Y5P4
PHAROS:  Q9Y5P4
GTEx:  ENSG00000113163 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y5P4
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
16C
Query on 16C

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
N-((E,2S,3R)-1,3-DIHYDROXYOCTADEC-4-EN-2-YL)PALMITAMIDE
C34 H67 N O3
YDNKGFDKKRUKPY-TURZORIXSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.219 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 45.976α = 77.72
b = 49.699β = 71.06
c = 62.365γ = 82.1
Software Package:
Software NamePurpose
MOLREPphasing
REFMACrefinement
HKL-2000data collection
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-12-18
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-03-13
    Changes: Data collection, Database references, Derived calculations, Structure summary