2X2C

acetyl-CypA:cyclosporine complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.41 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.209 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Acetylation Regulates Cyclophilin a Catalysis, Immunosuppression and HIV Isomerisation

Lammers, M.Neumann, H.Chin, J.W.James, L.C.

(2010) Nat Chem Biol 6: 331

  • DOI: https://doi.org/10.1038/nchembio.342
  • Primary Citation of Related Structures:  
    2X25, 2X2A, 2X2C, 2X2D

  • PubMed Abstract: 

    Cyclophilin A (CypA) is a ubiquitous cis-trans prolyl isomerase with key roles in immunity and viral infection. CypA suppresses T-cell activation through cyclosporine complexation and is required for effective HIV-1 replication in host cells. We show that CypA is acetylated in diverse human cell lines and use a synthetically evolved acetyllysyl-tRNA synthetase/tRNA(CUA) pair to produce recombinant acetylated CypA in Escherichia coli. We determined atomic-resolution structures of acetylated CypA and its complexes with cyclosporine and HIV-1 capsid. Acetylation markedly inhibited CypA catalysis of cis to trans isomerization and stabilized cis rather than trans forms of the HIV-1 capsid. Furthermore, CypA acetylation antagonized the immunosuppressive effects of cyclosporine by inhibiting the sequential steps of cyclosporine binding and calcineurin inhibition. Our results reveal that acetylation regulates key functions of CypA in immunity and viral infection and provide a general set of mechanisms by which acetylation modulates interactions to regulate cell function.


  • Organizational Affiliation

    Medical Research Council Laboratory of Molecular Biology, Protein and Nucleic Acid Chemistry Division, Cambridge, UK.


Macromolecules

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CYCLOSPORIN AA [auth B],
B [auth F],
D [auth L],
G [auth P],
I [auth R]
11Tolypocladium inflatumMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
PEPTIDYL-PROLYL CIS-TRANS ISOMERASE AC [auth K],
E [auth M],
F [auth O],
H [auth Q],
J [auth S]
165Homo sapiensMutation(s): 0 
EC: 5.2.1.8
UniProt & NIH Common Fund Data Resources
Find proteins for P62937 (Homo sapiens)
Explore P62937 
Go to UniProtKB:  P62937
PHAROS:  P62937
GTEx:  ENSG00000196262 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP62937
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  6 Unique
IDChains TypeFormula2D DiagramParent
ABA
Query on ABA
A [auth B],
B [auth F],
D [auth L],
G [auth P],
I [auth R]
L-PEPTIDE LINKINGC4 H9 N O2ALA
BMT
Query on BMT
A [auth B],
B [auth F],
D [auth L],
G [auth P],
I [auth R]
L-PEPTIDE LINKINGC10 H19 N O3THR
MLE
Query on MLE
A [auth B],
B [auth F],
D [auth L],
G [auth P],
I [auth R]
L-PEPTIDE LINKINGC7 H15 N O2LEU
MVA
Query on MVA
A [auth B],
B [auth F],
D [auth L],
G [auth P],
I [auth R]
L-PEPTIDE LINKINGC6 H13 N O2VAL
SAR
Query on SAR
A [auth B],
B [auth F],
D [auth L],
G [auth P],
I [auth R]
PEPTIDE LINKINGC3 H7 N O2GLY
ALY
Query on ALY
C [auth K],
E [auth M],
F [auth O],
H [auth Q],
J [auth S]
L-PEPTIDE LINKINGC8 H16 N2 O3LYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.41 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.209 
  • Space Group: P 61 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 107.429α = 90
b = 107.429β = 90
c = 428.871γ = 120
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-03-23
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Atomic model, Database references, Derived calculations, Structure summary, Version format compliance
  • Version 1.2: 2011-10-26
    Changes: Database references
  • Version 1.3: 2012-11-30
    Changes: Other
  • Version 1.4: 2018-05-02
    Changes: Advisory, Data collection