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Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex.


ABSTRACT: The circadian clock in mammals is driven by an autoregulatory transcriptional feedback mechanism that takes approximately 24 hours to complete. A key component of this mechanism is a heterodimeric transcriptional activator consisting of two basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) domain protein subunits, CLOCK and BMAL1. Here, we report the crystal structure of a complex containing the mouse CLOCK:BMAL1 bHLH-PAS domains at 2.3 Å resolution. The structure reveals an unusual asymmetric heterodimer with the three domains in each of the two subunits--bHLH, PAS-A, and PAS-B--tightly intertwined and involved in dimerization interactions, resulting in three distinct protein interfaces. Mutations that perturb the observed heterodimer interfaces affect the stability and activity of the CLOCK:BMAL1 complex as well as the periodicity of the circadian oscillator. The structure of the CLOCK:BMAL1 complex is a starting point for understanding at an atomic level the mechanism driving the mammalian circadian clock.

SUBMITTER: Huang N 

PROVIDER: S-EPMC3694778 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex.

Huang Nian N   Chelliah Yogarany Y   Shan Yongli Y   Taylor Clinton A CA   Yoo Seung-Hee SH   Partch Carrie C   Green Carla B CB   Zhang Hong H   Takahashi Joseph S JS  

Science (New York, N.Y.) 20120531 6091


The circadian clock in mammals is driven by an autoregulatory transcriptional feedback mechanism that takes approximately 24 hours to complete. A key component of this mechanism is a heterodimeric transcriptional activator consisting of two basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) domain protein subunits, CLOCK and BMAL1. Here, we report the crystal structure of a complex containing the mouse CLOCK:BMAL1 bHLH-PAS domains at 2.3 Å resolution. The structure reveals an unusual asymmetric hete  ...[more]

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