Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex

Nian Huang, Yogarany Chelliah, Yongli Shan, Clinton A. Taylor, Seung Hee Yoo, Carrie Partch, Carla B. Green, Hong Zhang, Joseph S. Takahashi

Research output: Contribution to journalArticlepeer-review

224 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)189-194
Number of pages6
Issue number6091
StatePublished - Jul 13 2012

ASJC Scopus subject areas

  • General


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