Publication Abstract from PubMed
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 A 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.
Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex.,Huang N, Chelliah Y, Shan Y, Taylor CA, Yoo SH, Partch C, Green CB, Zhang H, Takahashi JS Science. 2012 Jul 13;337(6091):189-94. Epub 2012 May 31. PMID:22653727[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
