Circadian Clock Protein KaiC

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Contents 1 Introduction 2 KaiC - KaiA - KaiB System 3 KaiC Homohexameric Complex 4 KaiC Autophosphorylation Sites 5 KaiA <-> KaiC Interaction Site 6 KaiB <-> KaiC Interaction Site 7 Biological Importance

Introduction

Biological Circadian Clocks are self-sustaining oscillators that function on a rhythmic cycle of or around 24 hours. The are found in almost all organisms, the simplest of which are cyanobacteria, which have been extensively studied in order to determine the mechanism of the fine-tunes biological process of circadian rhythmicity.

KaiC - KaiA - KaiB System

KaiC is the central clock protein, which has autokinase and autophosphorylase activity. Yet in the presence of ATP, KaiC cannot perform it's autophosphorylation function. It requires two other proteins, KaiA and KaiB, the genes of which are found in the same cluster on the chromosome (1). Although KaiC phosphorylates itself, the presence of KaiA and KaiB are essential to rhythmicity. KaiA stimulates KaiC autophosphorylation, while KaiB antagonizes the process possibly by enhancing KaiC dephosphorylation. Even in the presence of high ATP, KaiB still prompts KaiC to dephosphorylate.

KaiC Homohexameric Complex

spinqualitylabelsall models Structure of KaiC (PDB entry 1TF7) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image The structure of KaiC resembles a double donut formation with a central pore through the center. It is comprised of two subunits, CI and CII, and each subunit is made up of six nearly homologous monomers. The entire molecule is massive, comprising of 519 amino acid residues, and spanning 100 Angstroms in diameter. The waist of the molecule (the region between CI and CII) has a diameter of 62 Angstroms. The central pore that runs through the molecule is wider at the CI subunit end, 22 Angstroms, and narrows to a nearly closed conformation appears to be secured by six arginine residues. Their basic, polar nature and untidiness of this region indicate the possibility of conformational change, such as closing and opening. (1)

KaiC Autophosphorylation Sites

(difference between ATP binding and phosphorylation residues) (Key residues = T432, S431, T426) (show 3D image of these sites and highlight bonds/interactions)

KaiA <-> KaiC Interaction Site

(show 3D image of KaiC site for KaiA binding and highlight key residues in interaction -weak? strong? any ions in site? how does it stabilize autophosporylation?) KaiA binds to the interface of the two donut-shaped KaiC subunits, CI and CII. This area, known as the "waist" of the molecule

KaiB <-> KaiC Interaction Site

(show 3D image of KaiC site for KaiB binding and highlight key residues in interaction -weak? strong? ions in site? how does it stabilize dephosphorylation/destabilize phosphorylation/destabilize KaiA?)

Biological Importance

- Nearly all promoters in a cyanobacteria are under circadian control. [function is important to whole life cycle] (1)