PMID:20364129

Citation	Lammers, M, Neumann, H, Chin, JW and James, LC (2010) Acetylation regulates cyclophilin A catalysis, immunosuppression and HIV isomerization. Nat. Chem. Biol. 6:331-7
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.
Links	PubMed PMC3867001 Online version:10.1038/nchembio.342
Keywords	Acetylation; Biocatalysis; Calcineurin/antagonists & inhibitors; Cell Line; Cyclophilin A/metabolism; Cyclosporine/metabolism; HIV-1/physiology; Humans; Immunosuppression; Isomerism; Models, Molecular; Virus Replication
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:PPIA		GO:0003755: peptidyl-prolyl cis-trans isomerase activity	ECO:0000314:		F		Figure 5 shows that through acetylation, the Cyclophilin A can be regulated by selecting for the cis-trans peptidyl-prolyl bond.	complete CACAO 9308

References

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