Download MendeleyCrystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex.
Huang, N., Chelliah, Y., Shan, Y., Taylor, C.A., Yoo, S.H., Partch, C., Green, C.B., Zhang, H., Takahashi, J.S.(2012) Science 337: 189-194
- PubMed: 22653727
- DOI: https://doi.org/10.1126/science.1222804
- Primary Citation of Related Structures:
4F3L - PubMed 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.
Organizational Affiliation:
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
