circadian kaic phosphorylation a multi-layer network昼夜kaic磷酸化多层网络.pdfVIP

Circadian KaiC Phosphorylation: A Multi-Layer Network Congxin Li, Xiaofang Chen, Pengye Wang, Weichi Wang* Laboratory of Soft Matter Physics, Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China Abstract Circadian KaiC phosphorylation in cyanobacteria reconstituted in vitro recently initiates a series of studies experimentally and theoretically to explore its mechanism. In this paper, we report a dynamic diversity in hexameric KaiC phosphoforms using a multi-layer reaction network based on the nonequivalence of the dual phosphorylation sites (S431 and T432) in each KaiC subunit. These diverse oscillatory profiles can generate a kaleidoscopic phase modulation pattern probably responsible for the genome-wide transcription rhythms directly and/or indirectly in cyanobacteria. Particularly, our model reveals that a single KaiC hexamer is an energy-based, phosphorylation-dependent and self-regulated circadian oscillator modulated by KaiA and KaiB. We suggest that T432 is the main regulator for the oscillation amplitude, while S431 is the major phase regulator. S431 and T432 coordinately control the phosphorylation period. Robustness of the Kai network was examined by mixing samples in different phases, and varying protein concentrations and temperature. Similar results were obtained regardless of the deterministic or stochastic method employed. Therefore, the dynamic diversities and robustness of Kai oscillator make it a qualified core pacemaker that controls the cellular processes in cyanobacteria pervasively and accurately. Citation: Li C, Chen X, Wang P, Wang W (2009) Circadian KaiC Phosphorylation: A Multi-Layer Network. PLoS Comput Biol 5(11): e1000568. doi:10.1371/ journal.pcbi.1000568 Editor: Jorg Stelling, ETH Zurich, Switzerland Received November 26, 2