4NEH

An internal ligand-bound, metastable state of a leukocyte integrin, aXb2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.194 

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Ligand Structure Quality Assessment 


This is version 3.2 of the entry. See complete history


Literature

An internal ligand-bound, metastable state of a leukocyte integrin, alpha X beta 2.

Sen, M.Yuki, K.Springer, T.A.

(2013) J Cell Biol 203: 629-642

  • DOI: https://doi.org/10.1083/jcb.201308083
  • Primary Citation of Related Structures:  
    4NEH, 4NEN

  • PubMed Abstract: 

    How is massive conformational change in integrins achieved on a rapid timescale? We report crystal structures of a metastable, putative transition state of integrin αXβ2. The αXβ2 ectodomain is bent; however, a lattice contact stabilizes its ligand-binding αI domain in a high affinity, open conformation. Much of the αI α7 helix unwinds, loses contact with the αI domain, and reshapes to form an internal ligand that binds to the interface between the β propeller and βI domains. Lift-off of the αI domain above this platform enables a range of extensional and rotational motions without precedent in allosteric machines. Movements of secondary structure elements in the β2 βI domain occur in an order different than in β3 integrins, showing that integrin β subunits can be specialized to assume different intermediate states between closed and open. Mutations demonstrate that the structure trapped here is metastable and can enable rapid equilibration between bent and extended-open integrin conformations and up-regulation of leukocyte adhesiveness.


  • Organizational Affiliation

    Program in Cellular and Molecular Medicine, 2 Department of Medicine, 3 Department of Anethesiology, 4 Children's Hospital Boston, and 5 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Integrin alpha-X1,094Homo sapiensMutation(s): 0 
Gene Names: ITGAXCD11C
UniProt & NIH Common Fund Data Resources
Find proteins for P20702 (Homo sapiens)
Explore P20702 
Go to UniProtKB:  P20702
PHAROS:  P20702
GTEx:  ENSG00000140678 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP20702
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Integrin beta-2686Homo sapiensMutation(s): 0 
Gene Names: ITGB2CD18MFI7
UniProt & NIH Common Fund Data Resources
Find proteins for P05107 (Homo sapiens)
Explore P05107 
Go to UniProtKB:  P05107
PHAROS:  P05107
GTEx:  ENSG00000160255 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP05107
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C, F, G, H
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
D
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
E
7N-Glycosylation
Glycosylation Resources
GlyTouCan:  G07617FP
GlyCosmos:  G07617FP
GlyGen:  G07617FP
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
M [auth A]2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
I [auth A],
K [auth A],
L [auth A],
P [auth B],
Q [auth B]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
N [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
MG
Query on MG

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J [auth A],
R [auth B]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
O [auth A]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.194 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 126.967α = 90
b = 131.444β = 90
c = 190.477γ = 90
Software Package:
Software NamePurpose
PHASERphasing
PHENIXrefinement
XDSdata reduction
XDSdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-01-15
    Type: Initial release
  • Version 2.0: 2020-06-03
    Changes: Atomic model, Data collection, Database references, Derived calculations
  • Version 3.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
  • Version 3.1: 2021-06-02
    Changes: Source and taxonomy, Structure summary
  • Version 3.2: 2023-09-20
    Changes: Data collection, Database references, Refinement description