Crystal Structure of Circadian Clock Protein KaiA from Synechococcus elongatus*

The circadian clock found in Synechococcus elongatus, the most ancient circadian clock, is regulated by the interaction of three proteins, KaiA, KaiB, and KaiC. While the precise function of these proteins remains unclear, KaiA has been shown to be a positive regulator of the expression of KaiB and KaiC. The 2.0-Å structure of KaiA of S. elongatus reported here shows that the protein is composed of two independently folded domains connected by a linker. The NH2-terminal pseudo-receiver domain has a similar fold with that of bacterial response regulators, whereas the COOH-terminal four-helix bundle domain is novel and forms the interface of the 2-fold-related homodimer. The COOH-terminal four-helix bundle domain has been shown to contain the KaiC binding site. The structure suggests that the KaiB binding site is covered in the dimer interface of the KaiA “closed” conformation, observed in the crystal structure, which suggests an allosteric regulation mechanism.

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