4F3L

Crystal Structure of the Heterodimeric CLOCK:BMAL1 Transcriptional Activator Complex

Summary for 4F3L

• Entry DOI: 10.2210/pdb4f3l/pdb
• Descriptor: BMAL1b, Circadian locomoter output cycles protein kaput (3 entities in total)
• Functional Keywords: bhlh, pas, circadian rhythm proteins, transcription-activator complex, transcription/activator
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 2
• Total formula weight: 86276.09

Authors

Huang, N.,Chelliah, Y.,Shan, Y.,Taylor, C.,Yoo, S.,Partch, C.,Green, C.B.,Zhang, H.,Takahashi, J. (deposition date: 2012-05-09, release date: 2012-06-06, Last modification date: 2024-02-28)

Primary citation

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

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.

PubMed: 22653727
DOI: 10.1126/science.1222804

Experimental method

X-RAY DIFFRACTION (2.268 Å)