The interaction between the catalytic A subunit of calcineurin and its autoinhibitory domain, in the yeast two‐hybrid system, is disrupted by cyclosporin A and FK506

FEBS Letters

Hämmerle, Marcus¹  Chaudhuri, Bhabatosh¹  Fürst, Peter¹ 

[1] Department of Core Drug Discovery Technologies (CDDT), K-681. 1.46, Ciba-Geigy Ltd., CH-4002 Basel, Switzerland

关键词: Autoinhibitory domain;    Calcineurin;    Cyclosporin A;    FK506;    Inhibitor;    Yeast two-hybrid system;    AID;    autoinhibitory domain;    Cna1;    protein coding for the catalytic A subunit of yeast calcineurin;    Cna2;    protein coding for the second A subunit of yeast calcineurin;    Cnb1;    protein coding for the regulatory B subunit of yeast calcineurin;    CsA;    cyclosporin A;    FKBP;    FK506-binding protein;    PCR;    polymerase chain reaction;    SUC2t;    transcription terminator from the yeast SUC2 gene;   

DOI  :  10.1016/0014-5793(94)01365-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The Ca²⁺-calmodulin dependent protein phosphatase, calcineurin, is thought to mediate the action of the two immuno-suppressants, cyclosporin A (CsA) and FK506. Calcineurin from all species consists of a catalytic A subunit and a regulatory peptide B, which plays an essential role in catalysis. The enzymatic function is probably also regulated by an autoinhibitory domain (AID) present in the catalytic subunit. We have used the yeast two-hybrid system to show that the putative AID of the yeast catalytic subunit Cna1 binds only to truncated Cna1, devoid of AID. Although deletion of the genes encoding the yeast catalytic subunits of calcineurin (CNA1 and CNA2) maintain the interaction, absence of the regulatory subunit Cnb1 prevents binding. Interestingly, both CsA and FK506 disrupt this interaction, whereas binding of Cna1 to calmodulin remains unaffected. This indicates that a simple cellular system, developed in yeast, could provide further insight into an understanding of calcineurin inhibition.

【 授权许可】

Unknown