3Q03

Crystal structure of plasminogen activator inhibitor-1 in a metastable active conformation.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.64 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.174 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Crystal structure of plasminogen activator inhibitor-1 in an active conformation with normal thermodynamic stability.

Jensen, J.K.Thompson, L.C.Bucci, J.C.Nissen, P.Gettins, P.G.Peterson, C.B.Andreasen, P.A.Morth, J.P.

(2011) J Biol Chem 286: 29709-29717

  • DOI: https://doi.org/10.1074/jbc.M111.236554
  • Primary Citation of Related Structures:  
    3Q02, 3Q03

  • PubMed Abstract: 

    The serpin plasminogen activator inhibitor-1 (PAI-1) is a crucial regulator in fibrinolysis and tissue remodeling. PAI-1 has been associated with several pathological conditions and is a validated prognostic marker in human cancers. However, structural information about the native inhibitory form of PAI-1 has been elusive because of its inherent conformational instability and rapid conversion to a latent, inactive structure. Here we report the crystal structure of PAI-1 W175F at 2.3 Å resolution as the first model of the metastable native molecule. Structural comparison with a quadruple mutant (14-1B) previously used as representative of the active state uncovered key differences. The most striking differences occur near the region that houses three of the four mutations in the 14-1B PAI-1 structure. Prominent changes are localized within a loop connecting β-strand 3A with the F helix, in which a previously observed 3(10)-helix is absent in the new structure. Notably these structural changes are found near the binding site for the cofactor vitronectin. Because vitronectin is the only known physiological regulator of PAI-1 that slows down the latency conversion, the structure of this region is important. Furthermore, the previously identified chloride-binding site close to the F-helix is absent from the present structure and likely to be artifactual, because of its dependence on the 14-1B mutations. Instead we found a different chlorine-binding site that is likely to be present in wild type PAI-1 and that more satisfactorily accounts for the chlorine stabilizing effect on PAI-1.


  • Organizational Affiliation

    Department of Molecular Biology, Aarhus University, Aarhus C, Denmark. jkj@mb.au.dk


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Plasminogen activator inhibitor 1
A, B
379Homo sapiensMutation(s): 1 
Gene Names: PAI1PLANH1SERPINE1
UniProt & NIH Common Fund Data Resources
Find proteins for P05121 (Homo sapiens)
Explore P05121 
Go to UniProtKB:  P05121
PHAROS:  P05121
GTEx:  ENSG00000106366 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP05121
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.64 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.174 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 76.68α = 90
b = 67.16β = 100.45
c = 91.16γ = 90
Software Package:
Software NamePurpose
PHASERphasing
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-06-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-08-10
    Changes: Database references
  • Version 1.3: 2011-09-07
    Changes: Database references
  • Version 1.4: 2017-11-08
    Changes: Refinement description
  • Version 1.5: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description