Molecular Playground/CLOCK:BMAL1 heterodimer complex

The CLOCK:BMAL1 heterodimer complex is a vital regulatory component of the circadian rhythm protein regulation system.

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CLOCK

CLOCK is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. ^[1]

BMAL1

Heterodimer complex

Circadian Rhythm

The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCL:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels. ^[2]

Disease

Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result.

Relevance

Structural highlights

and will form a heterodimer complex.

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