4KZV

Structure of the carbohydrate-recognition domain of the C-type lectin mincle bound to trehalose


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.170 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Mechanism for Recognition of an Unusual Mycobacterial Glycolipid by the Macrophage Receptor Mincle.

Feinberg, H.Jegouzo, S.A.Rowntree, T.J.Guan, Y.Brash, M.A.Taylor, M.E.Weis, W.I.Drickamer, K.

(2013) J Biol Chem 288: 28457-28465

  • DOI: 10.1074/jbc.M113.497149
  • Primary Citation of Related Structures:  
    4KZV, 4KZW

  • PubMed Abstract: 
  • Binding of the macrophage lectin mincle to trehalose dimycolate, a key glycolipid virulence factor on the surface of Mycobacterium tuberculosis and Mycobacterium bovis, initiates responses that can lead both to toxicity and to protection of these pathogens from destruction ...

    Binding of the macrophage lectin mincle to trehalose dimycolate, a key glycolipid virulence factor on the surface of Mycobacterium tuberculosis and Mycobacterium bovis, initiates responses that can lead both to toxicity and to protection of these pathogens from destruction. Crystallographic structural analysis, site-directed mutagenesis, and binding studies with glycolipid mimics have been used to define an extended binding site in the C-type carbohydrate recognition domain (CRD) of bovine mincle that encompasses both the headgroup and a portion of the attached acyl chains. One glucose residue of the trehalose Glcα1-1Glcα headgroup is liganded to a Ca(2+) in a manner common to many C-type CRDs, whereas the second glucose residue is accommodated in a novel secondary binding site. The additional contacts in the secondary site lead to a 36-fold higher affinity for trehalose compared with glucose. An adjacent hydrophobic groove, not seen in other C-type CRDs, provides a docking site for one of the acyl chains attached to the trehalose, which can be targeted with small molecule analogs of trehalose dimycolate that bind with 52-fold higher affinity than trehalose. The data demonstrate how mincle bridges between the surfaces of the macrophage and the mycobacterium and suggest the possibility of disrupting this interaction. In addition, the results may provide a basis for design of adjuvants that mimic the ability of mycobacteria to stimulate a response to immunization that can be employed in vaccine development.


    Organizational Affiliation

    From the Departments of Structural Biology and Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305 and.



Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChainsSequence LengthOrganismDetailsImage
C-type lectin mincleA, B134Bos taurusMutation(s): 0 
Gene Names: CLEC4E
UniProt
Find proteins for E1BHM0 (Bos taurus)
Explore E1BHM0 
Go to UniProtKB:  E1BHM0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupE1BHM0
Protein Feature View
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChainsChain Length2D DiagramGlycosylation3D Interactions
alpha-D-glucopyranose-(1-1)-alpha-D-glucopyranoseC 2N/A Oligosaccharides Interaction
Glycosylation Resources
GlyTouCan:  G92130SN
GlyCosmos:  G92130SN
Small Molecules
Biologically Interesting Molecules (External Reference) 1 Unique
Entity ID: 2
IDChainsNameType/Class2D Diagram3D Interactions
PRD_900006
Query on PRD_900006
CtrehaloseOligosaccharide / Nutrient Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.170 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 73.48α = 90
b = 73.48β = 90
c = 99.34γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
Blu-Icedata collection
XDSdata reduction
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-08-28
    Type: Initial release
  • Version 1.1: 2013-09-04
    Changes: Database references
  • Version 1.2: 2013-10-23
    Changes: Database references
  • Version 1.3: 2017-11-15
    Changes: Refinement description
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Structure summary