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

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.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIHOTHER
OSTI Identifier:
1375362
Resource Type:
Journal Article
Resource Relation:
Journal Name: Structure; Journal Volume: 25; Journal Issue: 8
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Hou, Zhiqiang, Su, Lijing, Pei, Jimin, Grishin, Nick V., and Zhang, Hong. Crystal Structure of the CLOCK Transactivation Domain Exon19 in Complex with a Repressor. United States: N. p., 2017. Web. doi:10.1016/j.str.2017.05.023.
Hou, Zhiqiang, Su, Lijing, Pei, Jimin, Grishin, Nick V., & Zhang, Hong. Crystal Structure of the CLOCK Transactivation Domain Exon19 in Complex with a Repressor. United States. doi:10.1016/j.str.2017.05.023.
Hou, Zhiqiang, Su, Lijing, Pei, Jimin, Grishin, Nick V., and Zhang, Hong. Tue . "Crystal Structure of the CLOCK Transactivation Domain Exon19 in Complex with a Repressor". United States. doi:10.1016/j.str.2017.05.023.
@article{osti_1375362,
title = {Crystal Structure of the CLOCK Transactivation Domain Exon19 in Complex with a Repressor},
author = {Hou, Zhiqiang and Su, Lijing and Pei, Jimin and Grishin, Nick V. and Zhang, Hong},
abstractNote = {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.},
doi = {10.1016/j.str.2017.05.023},
journal = {Structure},
number = 8,
volume = 25,
place = {United States},
year = {Tue Aug 01 00:00:00 EDT 2017},
month = {Tue Aug 01 00:00:00 EDT 2017}
}