4o0m

Structural highlights

Function

KAIC_THEVB Central component of the KaiABC oscillator complex, which constitutes the main circadian regulator in cyanobacteria. Complex composition changes during the circadian cycle to control KaiC phosphorylation. KaiA stimulates KaiC autophosphorylation, while KaiB sequesters KaiA, leading to KaiC autodephosphorylation. Clock output pathways impact the RpaA transcriptional regulator. KaiC enhances the autophosphorylation activity of SasA, which then transfers its phosphate group to RpaA to activate it. KaiB and KaiC together enhance the phospho-RpaA dephosphatase activity of CikA.[HAMAP-Rule:MF_01836] Stimulates SasA autophosphorylation. Fully phosphorylated KaiC (tested with phosphomimetic Asp-431-432-Asp) is the best stimulant, requires the ATPase activity of the CII domain. Unphosphorylated SasA associates with KaiC and its autophosphorylation activity is enhanced. Phospho-SasA is released and associates with RpaA, transferring its phosphate group (PubMed:22512339). Formation of the KaiA:KaiB complex is promoted by KaiC, helping switch KaiC from its autophosphorylation to autodephosphatase function (PubMed:24112939, PubMed:28302851).^{[1] [2] [3]} Has a weak, temperature-independent ATPase activity (about 14 molecules of ATP per day) that defines the circadian period (PubMed:28302851, PubMed:34618577). ATPase activity is mostly contributed by the CI domain; the CII domain augments the activity. The addition of KaiA increases activity. ATPase is inhibited during the KaiC phosphorylating phase and activated during the KaiC dephosphorylating phase (PubMed:35507871).^{[4] [5] [6]}

See Also

• Circadian clock protein 3D structures

References

1. ↑ Valencia S J, Bitou K, Ishii K, Murakami R, Morishita M, Onai K, Furukawa Y, Imada K, Namba K, Ishiura M. Phase-dependent generation and transmission of time information by the KaiABC circadian clock oscillator through SasA-KaiC interaction in cyanobacteria. Genes Cells. 2012 May;17(5):398-419. PMID:22512339 doi:10.1111/j.1365-2443.2012.01597.x
2. ↑ Tseng R, Chang YG, Bravo I, Latham R, Chaudhary A, Kuo NW, Liwang A. Cooperative KaiA-KaiB-KaiC interactions affect KaiB/SasA competition in the circadian clock of cyanobacteria. J Mol Biol. 2014 Jan 23;426(2):389-402. PMID:24112939 doi:10.1016/j.jmb.2013.09.040
3. ↑ Tseng R, Goularte NF, Chavan A, Luu J, Cohen SE, Chang YG, Heisler J, Li S, Michael AK, Tripathi S, Golden SS, LiWang A, Partch CL. Structural basis of the day-night transition in a bacterial circadian clock. Science. 2017 Mar 17;355(6330):1174-1180. doi: 10.1126/science.aag2516. Epub 2017, Mar 16. PMID:28302851 doi:http://dx.doi.org/10.1126/science.aag2516
4. ↑ Tseng R, Goularte NF, Chavan A, Luu J, Cohen SE, Chang YG, Heisler J, Li S, Michael AK, Tripathi S, Golden SS, LiWang A, Partch CL. Structural basis of the day-night transition in a bacterial circadian clock. Science. 2017 Mar 17;355(6330):1174-1180. doi: 10.1126/science.aag2516. Epub 2017, Mar 16. PMID:28302851 doi:http://dx.doi.org/10.1126/science.aag2516
5. ↑ Chavan AG, Swan JA, Heisler J, Sancar C, Ernst DC, Fang M, Palacios JG, Spangler RK, Bagshaw CR, Tripathi S, Crosby P, Golden SS, Partch CL, LiWang A. Reconstitution of an intact clock reveals mechanisms of circadian timekeeping. Science. 2021 Oct 8;374(6564):eabd4453. PMID:34618577 doi:10.1126/science.abd4453
6. ↑ Furuike Y, Mukaiyama A, Koda SI, Simon D, Ouyang D, Ito-Miwa K, Saito S, Yamashita E, Nishiwaki-Ohkawa T, Terauchi K, Kondo T, Akiyama S. Regulation mechanisms of the dual ATPase in KaiC. Proc Natl Acad Sci U S A. 2022 May 10;119(19):e2119627119. PMID:35507871 doi:10.1073/pnas.2119627119