Crystal Structure of the CLOCK Transactivation Domain Exon19 in Complex with a Repressor

Zhiqiang Hou, Lijing Su, Jimin Pei, Nick V. Grishin, Hong Zhang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1187-1194.e3
JournalStructure
Volume25
Issue number8
DOIs
StatePublished - Aug 1 2017

Keywords

  • CIPC
  • CLOCK protein
  • Drosophila clock
  • circadian rhythm
  • coiled coil
  • crystal structure
  • repressor
  • transcription activation

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Crystal Structure of the CLOCK Transactivation Domain Exon19 in Complex with a Repressor'. Together they form a unique fingerprint.

Cite this