Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1
Abstract
The basic helix-loop-helix PAS domain (bHLH-PAS) transcription factor CLOCK:BMAL1 (brain and muscle Arnt-like protein 1) sits at the core of the mammalian circadian transcription/translation feedback loop. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ~24-h periodicity of gene expression. Formation of a repressive complex, defined by the core clock proteins cryptochrome 1 (CRY1):CLOCK:BMAL1, plays an important role controlling the switch from repression to activation each day. Here in this paper, we show that CRY1 binds directly to the PAS domain core of CLOCK: BMAL1, driven primarily by interaction with the CLOCK PAS-B domain. Integrative modeling and solution X-ray scattering studies unambiguously position a key loop of the CLOCK PAS-B domain in the secondary pocket of CRY1, analogous to the antenna chromophore-binding pocket of photolyase. CRY1 docks onto the transcription factor alongside the PAS domains, extending above the DNA-binding bHLH domain. Single point mutations at the interface on either CRY1 or CLOCK disrupt formation of the ternary complex, highlighting the importance of this interface for direct regulation of CLOCK:BMAL1 activity by CRY1.
- Authors:
-
[1];
- Univ. of California, Santa Cruz, CA (United States). Dept. of Chemistry and Biochemistry
- Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Neuroscience; Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Howard Hughes Medical Inst.
- Univ. of California, Santa Cruz, CA (United States). Dept. of Chemistry and Biochemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division
- Hebrew Univ. of Jerusalem (Israel). School of Computer Science and Engineering, Inst. of Life Sciences
- Univ. of California, Santa Cruz, CA (United States). Dept. of Chemistry and Biochemistry; Univ. of California, San Diego, CA (United States). Center for Circadian Biology
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); National Institutes of Health (NIH)
- OSTI Identifier:
- 1379737
- Grant/Contract Number:
- AC02-05CH11231; GM107069
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 114; Journal Issue: 7; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences, Washington, DC (United States)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; integrative modeling; PAS domains; cryptochrome; circadian rhythms
Citation Formats
Michael, Alicia K., Fribourgh, Jennifer L., Chelliah, Yogarany, Sandate, Colby R., Hura, Greg L., Schneidman-Duhovny, Dina, Tripathi, Sarvind M., Takahashi, Joseph S., and Partch, Carrie L. Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1. United States: N. p., 2017.
Web. doi:10.1073/pnas.1615310114.
Michael, Alicia K., Fribourgh, Jennifer L., Chelliah, Yogarany, Sandate, Colby R., Hura, Greg L., Schneidman-Duhovny, Dina, Tripathi, Sarvind M., Takahashi, Joseph S., & Partch, Carrie L. Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1. United States. https://doi.org/10.1073/pnas.1615310114
Michael, Alicia K., Fribourgh, Jennifer L., Chelliah, Yogarany, Sandate, Colby R., Hura, Greg L., Schneidman-Duhovny, Dina, Tripathi, Sarvind M., Takahashi, Joseph S., and Partch, Carrie L. Tue .
"Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1". United States. https://doi.org/10.1073/pnas.1615310114. https://www.osti.gov/servlets/purl/1379737.
@article{osti_1379737,
title = {Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1},
author = {Michael, Alicia K. and Fribourgh, Jennifer L. and Chelliah, Yogarany and Sandate, Colby R. and Hura, Greg L. and Schneidman-Duhovny, Dina and Tripathi, Sarvind M. and Takahashi, Joseph S. and Partch, Carrie L.},
abstractNote = {The basic helix-loop-helix PAS domain (bHLH-PAS) transcription factor CLOCK:BMAL1 (brain and muscle Arnt-like protein 1) sits at the core of the mammalian circadian transcription/translation feedback loop. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ~24-h periodicity of gene expression. Formation of a repressive complex, defined by the core clock proteins cryptochrome 1 (CRY1):CLOCK:BMAL1, plays an important role controlling the switch from repression to activation each day. Here in this paper, we show that CRY1 binds directly to the PAS domain core of CLOCK: BMAL1, driven primarily by interaction with the CLOCK PAS-B domain. Integrative modeling and solution X-ray scattering studies unambiguously position a key loop of the CLOCK PAS-B domain in the secondary pocket of CRY1, analogous to the antenna chromophore-binding pocket of photolyase. CRY1 docks onto the transcription factor alongside the PAS domains, extending above the DNA-binding bHLH domain. Single point mutations at the interface on either CRY1 or CLOCK disrupt formation of the ternary complex, highlighting the importance of this interface for direct regulation of CLOCK:BMAL1 activity by CRY1.},
doi = {10.1073/pnas.1615310114},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 7,
volume = 114,
place = {United States},
year = {2017},
month = {1}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 10 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
PERIOD1-Associated Proteins Modulate the Negative Limb of the Mammalian Circadian Oscillator
journal, April 2005
- Brown, S. A.
- Science, Vol. 308, Issue 5722
Rhythmic PER Abundance Defines a Critical Nodal Point for Negative Feedback within the Circadian Clock Mechanism
journal, November 2009
- Chen, Rongmin; Schirmer, Aaron; Lee, Yongjin
- Molecular Cell, Vol. 36, Issue 3
Differential regulation of mammalian Period genes and circadian rhythmicity by cryptochromes 1 and 2
journal, October 1999
- Vitaterna, M. H.; Selby, C. P.; Todo, T.
- Proceedings of the National Academy of Sciences, Vol. 96, Issue 21
Transcriptional Architecture and Chromatin Landscape of the Core Circadian Clock in Mammals
journal, August 2012
- Koike, N.; Yoo, S. -H.; Huang, H. -C.
- Science, Vol. 338, Issue 6105
Solving structures of protein complexes by molecular replacement with Phaser
journal, December 2006
- McCoy, Airlie J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 63, Issue 1
Cryptochrome 1 regulates the circadian clock through dynamic interactions with the BMAL1 C terminus
journal, May 2015
- Xu, Haiyan; Gustafson, Chelsea L.; Sammons, Patrick J.
- Nature Structural & Molecular Biology, Vol. 22, Issue 6
Structural Basis of ARNT PAS-B Dimerization: Use of a Common Beta-sheet Interface for Hetero- and Homodimerization
journal, October 2005
- Card, Paul B.; Erbel, Paul J. A.; Gardner, Kevin H.
- Journal of Molecular Biology, Vol. 353, Issue 3
Macromolecular docking restrained by a small angle X-ray scattering profile
journal, March 2011
- Schneidman-Duhovny, Dina; Hammel, Michal; Sali, Andrej
- Journal of Structural Biology, Vol. 173, Issue 3
Molecular assembly of the period-cryptochrome circadian transcriptional repressor complex
journal, August 2014
- Nangle, Shannon N.; Rosensweig, Clark; Koike, Nobuya
- eLife, Vol. 3
Allosteric inhibition of hypoxia inducible factor-2 with small molecules
journal, February 2013
- Scheuermann, Thomas H.; Li, Qiming; Ma, He-Wen
- Nature Chemical Biology, Vol. 9, Issue 4
X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution
journal, August 2007
- Putnam, Christopher D.; Hammel, Michal; Hura, Greg L.
- Quarterly Reviews of Biophysics, Vol. 40, Issue 3
Accurate SAXS Profile Computation and its Assessment by Contrast Variation Experiments
journal, August 2013
- Schneidman-Duhovny, Dina; Hammel, Michal; Tainer, John A.
- Biophysical Journal, Vol. 105, Issue 4
The Second Chromophore in Drosophila Photolyase/Cryptochrome Family Photoreceptors
journal, December 2011
- Selby, Christopher P.; Sancar, Aziz
- Biochemistry, Vol. 51, Issue 1
Comparative Protein Structure Modeling Using MODELLER
journal, September 2014
- Webb, Benjamin; Sali, Andrej
- Current Protocols in Bioinformatics, Vol. 47, Issue 1
FoXS, FoXSDock and MultiFoXS: Single-state and multi-state structural modeling of proteins and their complexes based on SAXS profiles
journal, May 2016
- Schneidman-Duhovny, Dina; Hammel, Michal; Tainer, John A.
- Nucleic Acids Research, Vol. 44, Issue W1
Structure and Function of DNA Photolyase and Cryptochrome Blue-Light Photoreceptors
journal, June 2003
- Sancar, Aziz
- Chemical Reviews, Vol. 103, Issue 6
Crystal Structure of the Heterodimeric CLOCK:BMAL1 Transcriptional Activator Complex
journal, May 2012
- Huang, N.; Chelliah, Y.; Shan, Y.
- Science, Vol. 337, Issue 6091
Emerging Models for the Molecular Basis of Mammalian Circadian Timing
journal, December 2014
- Gustafson, Chelsea L.; Partch, Carrie L.
- Biochemistry, Vol. 54, Issue 2
Coactivators necessary for transcriptional output of the hypoxia inducible factor, HIF, are directly recruited by ARNT PAS-B
journal, April 2011
- Partch, C. L.; Gardner, K. H.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 19
The CCP4 suite programs for protein crystallography
journal, September 1994
- ,
- Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 5, p. 760-763
Dual modes of CLOCK:BMAL1 inhibition mediated by Cryptochrome and Period proteins in the mammalian circadian clock
journal, September 2014
- Ye, Rui; Selby, Cristopher P.; Chiou, Yi-Ying
- Genes & Development, Vol. 28, Issue 18
Animal Cryptochromes: Divergent Roles in Light Perception, Circadian Timekeeping and Beyond
journal, January 2017
- Michael, Alicia K.; Fribourgh, Jennifer L.; Van Gelder, Russell N.
- Photochemistry and Photobiology, Vol. 93, Issue 1
The genetics of mammalian circadian order and disorder: implications for physiology and disease
journal, October 2008
- Takahashi, Joseph S.; Hong, Hee-Kyung; Ko, Caroline H.
- Nature Reviews Genetics, Vol. 9, Issue 10
UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004
- Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
- Journal of Computational Chemistry, Vol. 25, Issue 13
Structural basis for PAS domain heterodimerization in the basic helix-loop-helix-PAS transcription factor hypoxia-inducible factor
journal, December 2003
- Erbel, P. J. A.; Card, P. B.; Karakuzu, O.
- Proceedings of the National Academy of Sciences, Vol. 100, Issue 26
Stoichiometric Relationship among Clock Proteins Determines Robustness of Circadian Rhythms
journal, January 2011
- Lee, Yongjin; Chen, Rongmin; Lee, Hyeong-min
- Journal of Biological Chemistry, Vol. 286, Issue 9
Quantitative Analyses of Cryptochrome-mBMAL1 Interactions: MECHANISTIC INSIGHTS INTO THE TRANSCRIPTIONAL REGULATION OF THE MAMMALIAN CIRCADIAN CLOCK
journal, April 2011
- Czarna, Anna; Breitkreuz, Helena; Mahrenholz, Carsten C.
- Journal of Biological Chemistry, Vol. 286, Issue 25
Electron Transfer Mechanisms of DNA Repair by Photolyase
journal, April 2015
- Zhong, Dongping
- Annual Review of Physical Chemistry, Vol. 66, Issue 1
Identification of a Novel Cryptochrome Differentiating Domain Required for Feedback Repression in Circadian Clock Function
journal, June 2012
- Khan, Sanjoy K.; Xu, Haiyan; Ukai-Tadenuma, Maki
- Journal of Biological Chemistry, Vol. 287, Issue 31
SCFFBXL3 ubiquitin ligase targets cryptochromes at their cofactor pocket
journal, March 2013
- Xing, Weiman; Busino, Luca; Hinds, Thomas R.
- Nature, Vol. 496, Issue 7443
Coot model-building tools for molecular graphics
journal, November 2004
- Emsley, Paul; Cowtan, Kevin
- Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
FoXS: a web server for rapid computation and fitting of SAXS profiles
journal, May 2010
- Schneidman-Duhovny, D.; Hammel, M.; Sali, A.
- Nucleic Acids Research, Vol. 38, Issue Web Server
Specificity in Circadian Clock Feedback from Targeted Reconstitution of the NuRD Corepressor
journal, December 2014
- Kim, Jin Young; Kwak, Pieter Bas; Weitz, Charles J.
- Molecular Cell, Vol. 56, Issue 6
Molecular architecture of the mammalian circadian clock
journal, February 2014
- Partch, Carrie L.; Green, Carla B.; Takahashi, Joseph S.
- Trends in Cell Biology, Vol. 24, Issue 2
Interaction of Circadian Clock Proteins CRY1 and PER2 Is Modulated by Zinc Binding and Disulfide Bond Formation
journal, May 2014
- Schmalen, Ira; Reischl, Silke; Wallach, Thomas
- Cell, Vol. 157, Issue 5
PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
A circadian gene expression atlas in mammals: Implications for biology and medicine
journal, October 2014
- Zhang, Ray; Lahens, Nicholas F.; Ballance, Heather I.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 45
CIPC is a mammalian circadian clock protein without invertebrate homologues
journal, February 2007
- Zhao, Wen-Ning; Malinin, Nikolay; Yang, Fu-Chia
- Nature Cell Biology, Vol. 9, Issue 3
Structural and Functional Analyses of PAS Domain Interactions of the Clock Proteins Drosophila PERIOD and Mouse PERIOD2
journal, April 2009
- Hennig, Sven; Strauss, Holger M.; Vanselow, Katja
- PLoS Biology, Vol. 7, Issue 4
The HADDOCK2.2 Web Server: User-Friendly Integrative Modeling of Biomolecular Complexes
journal, February 2016
- van Zundert, G. C. P.; Rodrigues, J. P. G. L. M.; Trellet, M.
- Journal of Molecular Biology, Vol. 428, Issue 4
NMRPipe: A multidimensional spectral processing system based on UNIX pipes
journal, November 1995
- Delaglio, Frank; Grzesiek, Stephan; Vuister, GeertenW.
- Journal of Biomolecular NMR, Vol. 6, Issue 3
mCRY1 and mCRY2 Are Essential Components of the Negative Limb of the Circadian Clock Feedback Loop
journal, July 1999
- Kume, Kazuhiko; Zylka, Mark J.; Sriram, Sathyanarayanan
- Cell, Vol. 98, Issue 2
Mop3 Is an Essential Component of the Master Circadian Pacemaker in Mammals
journal, December 2000
- Bunger, Maureen K.; Wilsbacher, Lisa D.; Moran, Susan M.
- Cell, Vol. 103, Issue 7
HingeProt: Automated prediction of hinges in protein structures
journal, September 2007
- Emekli, Ugur; Schneidman-Duhovny, Dina; Wolfson, Haim J.
- Proteins: Structure, Function, and Bioinformatics, Vol. 70, Issue 4
Structures of Drosophila Cryptochrome and Mouse Cryptochrome1 Provide Insight into Circadian Function
journal, June 2013
- Czarna, Anna; Berndt, Alex; Singh, Hari Raj
- Cell, Vol. 153, Issue 6
Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms
journal, April 1999
- Horst, Gijsbertus T. J. van der; Muijtjens, Manja; Kobayashi, Kumiko
- Nature, Vol. 398, Issue 6728
Feedback repression is required for mammalian circadian clock function
journal, February 2006
- Sato, Trey K.; Yamada, Rikuhiro G.; Ukai, Hideki
- Nature Genetics, Vol. 38, Issue 3
Circadian Clock Control by SUMOylation of BMAL1
journal, August 2005
- Cardone, L.
- Science, Vol. 309, Issue 5739
Biochemical Analysis of the Canonical Model for the Mammalian Circadian Clock
journal, May 2011
- Ye, Rui; Selby, Christopher P.; Ozturk, Nuri
- Journal of Biological Chemistry, Vol. 286, Issue 29
The integration of macromolecular diffraction data
journal, December 2005
- Leslie, Andrew G. W.
- Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 1
HADDOCK: A Protein−Protein Docking Approach Based on Biochemical or Biophysical Information
journal, February 2003
- Dominguez, Cyril; Boelens, Rolf; Bonvin, Alexandre M. J. J.
- Journal of the American Chemical Society, Vol. 125, Issue 7
Unwinding the differences of the mammalian PERIOD clock proteins from crystal structure to cellular function
journal, February 2012
- Kucera, N.; Schmalen, I.; Hennig, S.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 9
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation
journal, February 2021
- Tillu, Vikas A.; Rae, James; Gao, Ya
- Nature Communications, Vol. 12, Issue 1
Multi-functionality of a tryptophan residue conserved in substrate-binding groove of GH19 chitinases
journal, January 2021
- Nagata, Takuya; Shinya, Shoko; Ohnuma, Takayuki
- Scientific Reports, Vol. 11, Issue 1
The Second Chromophore in Drosophila Photolyase/Cryptochrome Family Photoreceptors
text, January 2012
- Aziz, Sancar,; P., Selby, Christopher
- The University of North Carolina at Chapel Hill University Libraries
Comparative Protein Structure Modeling Using MODELLER
journal, November 2016
- Webb, Benjamin; Sali, Andrej
- Current Protocols in Protein Science, Vol. 86, Issue 1
Differential regulation of mammalian Period genes and circadian rhythmicity by cryptochromes 1 and 2
text, January 1999
- J., Miyazaki,; H., Niwa,; T., Todo,
- The University of North Carolina at Chapel Hill University Libraries
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Apollo - University of Cambridge Repository
Biochemical Analysis of the Canonical Model for the Mammalian Circadian Clock
text, January 2011
- Rui, Ye,; P., Selby, Christopher; Aziz, Sancar,
- The University of North Carolina at Chapel Hill University Libraries
Works referencing / citing this record:
An evolutionary hotspot defines functional differences between CRYPTOCHROMES
journal, March 2018
- Rosensweig, Clark; Reynolds, Kimberly A.; Gao, Peng
- Nature Communications, Vol. 9, Issue 1
Vertebrate-like CRYPTOCHROME 2 from monarch regulates circadian transcription via independent repression of CLOCK and BMAL1 activity
journal, August 2017
- Zhang, Ying; Markert, Matthew J.; Groves, Shayna C.
- Proceedings of the National Academy of Sciences, Vol. 114, Issue 36
Circadian repressors CRY1 and CRY2 broadly interact with nuclear receptors and modulate transcriptional activity
journal, July 2017
- Kriebs, Anna; Jordan, Sabine D.; Soto, Erin
- Proceedings of the National Academy of Sciences, Vol. 114, Issue 33
Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue-specific circadian networks
journal, December 2018
- Qu, Meng; Duffy, Tomas; Hirota, Tsuyoshi
- Proceedings of the National Academy of Sciences, Vol. 115, Issue 52
Regulating behavior with the flip of a translational switch
journal, December 2018
- Ceh-Pavia, Efraín; Partch, Carrie L.
- Proceedings of the National Academy of Sciences, Vol. 115, Issue 52
Chemical and structural analysis of a photoactive vertebrate cryptochrome from pigeon
journal, September 2019
- Zoltowski, Brian D.; Chelliah, Yogarany; Wickramaratne, Anushka
- Proceedings of the National Academy of Sciences, Vol. 116, Issue 39
Principles of the animal molecular clock learned from Neurospora
journal, February 2019
- Loros, Jennifer J.
- European Journal of Neuroscience, Vol. 51, Issue 1
Allosteric mechanism of the circadian protein Vivid resolved through Markov state model and machine learning analysis
journal, February 2019
- Zhou, Hongyu; Dong, Zheng; Verkhivker, Gennady
- PLOS Computational Biology, Vol. 15, Issue 2
Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing
journal, February 2020
- Fribourgh, Jennifer L.; Srivastava, Ashutosh; Sandate, Colby R.
- eLife, Vol. 9