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Title: Structure of the frequency-interacting RNA helicase: a protein interaction hub for the circadian clock

Abstract

In the Neurospora crassa circadian clock, a protein complex of frequency (FRQ), casein kinase 1a (CK1a), and the FRQ-interacting RNA Helicase (FRH) rhythmically represses gene expression by the white-collar complex (WCC). FRH crystal structures in several conformations and bound to ADP/RNA reveal differences between FRH and the yeast homolog Mtr4 that clarify the distinct role of FRH in the clock. The FRQ-interacting region at the FRH N-terminus has variable structure in the absence of FRQ. A known mutation that disrupts circadian rhythms (R806H) resides in a positively charged surface of the KOW domain, far removed from the helicase core. Here, we show that changes to other similarly located residues modulate interactions with the WCC and FRQ. A V142G substitution near the N-terminus also alters FRQ and WCC binding to FRH, but produces an unusual short clock period. Finally, these data support the assertion that FRH helicase activity does not play an essential role in the clock, but rather FRH acts to mediate contacts among FRQ, CK1a and the WCC through interactions involving its N-terminus and KOW module.

Authors:
; ; ; ; ; ; ORCiD logo
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH); USDOE
OSTI Identifier:
1274770
DOE Contract Number:
P41 GM103403; R01‐GM079679; F32‐GM099391; R35‐GM118022; R01‐GM34985; R35‐GM118021
Resource Type:
Journal Article
Resource Relation:
Journal Name: EMBO Journal; Journal Volume: 35; Journal Issue: 15
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Conrad, Karen S., Hurley, Jennifer M., Widom, Joanne, Ringelberg, Carol S., Loros, Jennifer J., Dunlap, Jay C., and Crane, Brian R.. Structure of the frequency-interacting RNA helicase: a protein interaction hub for the circadian clock. United States: N. p., 2016. Web. doi:10.15252/embj.201694327.
Conrad, Karen S., Hurley, Jennifer M., Widom, Joanne, Ringelberg, Carol S., Loros, Jennifer J., Dunlap, Jay C., & Crane, Brian R.. Structure of the frequency-interacting RNA helicase: a protein interaction hub for the circadian clock. United States. doi:10.15252/embj.201694327.
Conrad, Karen S., Hurley, Jennifer M., Widom, Joanne, Ringelberg, Carol S., Loros, Jennifer J., Dunlap, Jay C., and Crane, Brian R.. 2016. "Structure of the frequency-interacting RNA helicase: a protein interaction hub for the circadian clock". United States. doi:10.15252/embj.201694327.
@article{osti_1274770,
title = {Structure of the frequency-interacting RNA helicase: a protein interaction hub for the circadian clock},
author = {Conrad, Karen S. and Hurley, Jennifer M. and Widom, Joanne and Ringelberg, Carol S. and Loros, Jennifer J. and Dunlap, Jay C. and Crane, Brian R.},
abstractNote = {In the Neurospora crassa circadian clock, a protein complex of frequency (FRQ), casein kinase 1a (CK1a), and the FRQ-interacting RNA Helicase (FRH) rhythmically represses gene expression by the white-collar complex (WCC). FRH crystal structures in several conformations and bound to ADP/RNA reveal differences between FRH and the yeast homolog Mtr4 that clarify the distinct role of FRH in the clock. The FRQ-interacting region at the FRH N-terminus has variable structure in the absence of FRQ. A known mutation that disrupts circadian rhythms (R806H) resides in a positively charged surface of the KOW domain, far removed from the helicase core. Here, we show that changes to other similarly located residues modulate interactions with the WCC and FRQ. A V142G substitution near the N-terminus also alters FRQ and WCC binding to FRH, but produces an unusual short clock period. Finally, these data support the assertion that FRH helicase activity does not play an essential role in the clock, but rather FRH acts to mediate contacts among FRQ, CK1a and the WCC through interactions involving its N-terminus and KOW module.},
doi = {10.15252/embj.201694327},
journal = {EMBO Journal},
number = 15,
volume = 35,
place = {United States},
year = 2016,
month = 6
}
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