Editors' ChoiceCircadian Biology

A Timely Structure

Sci. Signal.  17 Jul 2012:
Vol. 5, Issue 233, pp. ec192
DOI: 10.1126/scisignal.2003393

The physiology and behavior of most organisms are inextricably aligned with the day/night cycle. In mammals, these daily rhythms are generated by a circadian clock encoded by transcriptional activators and repressors operating in a feedback loop that takes about 24 hours to complete. A key participant in this loop is a heterodimeric transcriptional activator consisting of the CLOCK and BMAL1 proteins. Huang et al. (see the Perspective by Crane) determined the crystal structure of a complex containing the PAS domains (implicated in protein-protein interactions) and the basic helix-loop-helix domains (implicated in DNA binding) from each protein. CLOCK and BMAL1 were observed to be tightly intertwined in an unusual asymmetric conformation, which may contribute to the stability and activity of the complex.

N. Huang, Y. Chelliah, Y. Shan, C. A. Taylor, S.-H. Yoo, C. Partch, C. B. Green, H. Zhang, J. S. Takahashi, Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex. Science 337, 189–194 (2012). [Abstract] [Full Text]

B. R. Crane, Nature's intricate clockwork. Science 337, 165–166 (2012). [Abstract] [Full Text]

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