2X2D

acetyl-CypA:HIV-1 N-term capsid domain complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.200 

wwPDB Validation   3D Report Full Report


This is version 1.3 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:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PEPTIDYL-PROLYL CIS-TRANS ISOMERASE AA [auth B],
B [auth C]
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
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
CAPSID PROTEIN P24C [auth D],
D [auth E]
147Human immunodeficiency virus 1Mutation(s): 0 
UniProt
Find proteins for P12497 (Human immunodeficiency virus type 1 group M subtype B (isolate NY5))
Explore P12497 
Go to UniProtKB:  P12497
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP12497
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
ALY
Query on ALY
A [auth B],
B [auth C]
L-PEPTIDE LINKINGC8 H16 N2 O3LYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.200 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 38.542α = 90
b = 109.995β = 101.11
c = 67.567γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

View Full Validation Report



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: Advisory, Version format compliance
  • Version 1.2: 2011-10-26
    Changes: Database references, Derived calculations
  • Version 1.3: 2018-01-24
    Changes: Source and taxonomy