Figure 4.

Domain organization of Cyr1 in Saccharomyces cerevisiae and Candida albicans. A schematic representation of the domains of Cyr1 from (A) S. cerevisiae and (B) C. albicans. Cyr1 is the adenylyl cyclase that converts ATP to cAMP and thereby activates PKA. This enzymatic activity primarily requires the cyclase domain of Cyr1. The other domains act as sensors of different proteins/signals to regulate cAMP production by the cyclase domain. The Gα-binding domain (GαBD) binds to the α subunit (Gpa2) of a G-protein; Ras association (RA) domain interacts with Ras proteins; the leucine-rich repeat (LRR) domain interacts with Hsp90 proteins via their co-chaperone, Sgt1; and the cyclase associated protein 1 (CAP1) binding domain (CBD) interacts with Srv2/CAP1 protein. The role of the protein phosphatase 2C (PP2C) domain is not known. In C. albicans, the LRR domain is activated by bacterial peptidoglycans and muramyl dipeptides (shown by bluearrow). Its cyclase domain can be activated independently by CO₂ (shown by bluearrow) and repressed by farnesol (represented by red flatheaded arrow). Hyperactive mutants of C. albicans Cyr1 (Cyr1^E1541K) can simultaneously bind Ras1 and CAP1. Double headed arrows represent protein–protein interactions.