5VJI

Crystal structure of the CLOCK Transcription Domain Exon19 in Complex with a Repressor

Summary for 5VJI

• Entry DOI: 10.2210/pdb5vji/pdb
• Descriptor: Circadian locomoter output cycles protein kaput, CLOCK-interacting pacemaker (3 entities in total)
• Functional Keywords: circadian rhythm, clock protein, transcription activation, repressor, coiled coil, cipc, circadian clock, transcription
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 6
• Total formula weight: 39195.83

Authors

Hou, Z.,Su, L.,Pei, J.,Grishin, N.V.,Zhang, H. (deposition date: 2017-04-19, release date: 2017-06-07, Last modification date: 2020-01-01)

Primary citation

Hou, Z.,Su, L.,Pei, J.,Grishin, N.V.,Zhang, H.
Crystal Structure of the CLOCK Transactivation Domain Exon19 in Complex with a Repressor.
Structure, 25:1187-1194.e3, 2017

PubMed Abstract: In the canonical clock model, CLOCK:BMAL1-mediated transcriptional activation is feedback regulated by its repressors CRY and PER and, in association with other coregulators, ultimately generates oscillatory gene expression patterns. How CLOCK:BMAL1 interacts with coregulator(s) is not well understood. Here we report the crystal structures of the mouse CLOCK transactivating domain Exon19 in complex with CIPC, a potent circadian repressor that functions independently of CRY and PER. The Exon19:CIPC complex adopts a three-helical coiled-coil bundle conformation containing two Exon19 helices and one CIPC. Unique to Exon19:CIPC, three highly conserved polar residues, Asn341 of CIPC and Gln544 of the two Exon19 helices, are located at the mid-section of the coiled-coil bundle interior and form hydrogen bonds with each other. Combining results from protein database search, sequence analysis, and mutagenesis studies, we discovered for the first time that CLOCK Exon19:CIPC interaction is a conserved transcription regulatory mechanism among mammals, fish, flies, and other invertebrates.

PubMed: 28669630
DOI: 10.1016/j.str.2017.05.023

Experimental method

X-RAY DIFFRACTION (1.86 Å)