2X2C: acetyl-CypA:cyclosporine complex

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.
PDB ID: 2X2CDownload
MMDB ID: 161616
PDB Deposition Date: 2010/1/12
Updated in MMDB: 2018/05
Experimental Method:
x-ray diffraction
Resolution: 2.41  Å
Source Organism:
Similar Structures:
Biological Unit for 2X2C: eicosameric; determined by author and by software (PISA)
Molecular Components in 2X2C
Label Count Molecule
Proteins (10 molecules)
Peptidyl-prolyl Cis-trans Isomerase a(Gene symbol: PPIA)
Molecule annotation
Nucleotide(1 molecule)
Cyclosporin a
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB