Article
Multidisciplinary Sciences
Yoshihiko Furuike, Atsushi Mukaiyama, Shin-Ichi Koda, Damien Simon, Dongyan Ouyang, Kumiko Ito-Miwa, Shinji Saito, Eiki Yamashita, Taeko Nishiwaki-Ohkawa, Kazuki Terauchi, Takao Kondo, Shuji Akiyama
Summary: KaiC is a dual ATPase that drives the circadian clock system of cyanobacteria through the coordination of its N-terminal and C-terminal active sites. The activities of these two sites are regulated differently and their delicate interactions drive the assembly and disassembly cycle of KaiA and KaiB.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Mingxu Fang, Archana G. Chavan, Andy LiWang, Susan S. Golden
Summary: In this study, the researchers used the IVC reactions and massively parallel experiments to study entrainment, the synchronization of the circadian clock with the environment. The results showed that the IVC better explains the in vivo clock-resetting phenotypes of wild-type and mutant strains, and the output components are deeply engaged with the core oscillator, affecting the way input signals entrain the core pacemaker. These findings blur the line between input and output pathways and support the previous demonstration that key output components are fundamental parts of the clock.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Medicine, Research & Experimental
Yi Qin, Zhong-hua Chen, Jun-Jie Wu, Zhen-Yu Zhang, Zheng-Dong Yuan, Dan-Yang Guo, Meng-Nan Chen, Xia Li, Feng-Lai Yuan
Summary: The circadian clock plays a crucial role in regulating bone metabolism, including bone loss. Clock-related genes control signaling pathways and transcription factors in osteoblasts and osteoclasts, while also regulating osteocytes and endothelial cells. Furthermore, the regulation of circadian clock genes by novel modulators presents a potential strategy for preventing and treating bone diseases.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Xiaomeng Liu, Niuben Cao, Xinchan Liu, Yu Deng, Yu Xin, Ruobing Fu, Xirui Xin, Yubo Hou, Weixian Yu
Summary: Circadian rhythms play a crucial role in regulating the body's homeostasis, and circadian rhythm disorders can have detrimental effects on metabolic and immune functions. However, the relationship between circadian rhythm disorders and periodontitis has not been well studied. This research aimed to investigate the role of the circadian rhythm control gene BMAL1 in periodontitis. The results showed that downregulation of BMAL1 in circadian rhythm disorder-induced periodontitis led to significant alveolar bone resorption, increased osteoclast differentiation, upregulation of the inflammatory signaling molecule NF-kappa B, elevated apoptosis and oxidative stress levels in periodontal tissues. This study suggests that BMAL1 is a key regulator in periodontitis exacerbated by circadian rhythm disorders, highlighting a potential avenue for periodontitis treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Sabrina Klemz, Thomas Wallach, Sandra Korge, Mechthild Rosing, Roman Klemz, Bert Maier, Nicholas C. Fiorenza, Irem Kaymak, Anna K. Fritzsche, Erik D. Herzog, Ralf Stanewsky, Achim Kramer
Summary: In organisms with circadian clocks, the post-translational modifications of clock proteins, particularly phosphorylation, play a crucial role in controlling circadian rhythms. Protein phosphatase 4 (PPP4) and its regulatory subunit PPP4R2 have been identified as critical components in mammals and Drosophila, affecting the circadian system by regulating phosphorylation and transactivation activity of CLOCK/BMAL1.
GENES & DEVELOPMENT
(2021)
Editorial Material
Cell Biology
Ueli Schibler
Summary: Mammalian body cells have cell-autonomous and self-sustained circadian oscillators relying on delayed negative feedback loops in gene expression. Transcriptional activation and repression, as well as post-translational mechanisms like phosphorylation and dephosphorylation, play crucial roles in setting the pace of these timekeepers. The study by Klemz and colleagues in Genes & Development demonstrates how dephosphorylation of BMAL1 by protein phosphatase 4 (PPP4) participates in the modulation of circadian timing.
GENES & DEVELOPMENT
(2021)
Article
Multidisciplinary Sciences
Annika F. Barber, Shi Yi Fong, Anna Kolesnik, Michael Fetchko, Amita Sehgal
Summary: Regulation of circadian behavior and physiology by the Drosophila brain clock requires communication from central clock neurons to downstream output regions. Morning and evening clock neurons have time-of-day-dependent connectivity to the pars intercerebralis, which is regulated by specific peptides and fast neurotransmitters. This study provides insights into mechanisms by which clock neurons signal to nonclock cells to drive rhythms of behavior.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
Zainab Taleb, Phillip Karpowicz
Summary: The circadian clock is a molecular timekeeper that regulates 24-hour rhythms in animals, impacting behavior and physiology, including metabolic and digestive systems. Animal models targeting circadian clock genes have shown their role in regulating liver diseases, inflammatory bowel disease, colorectal cancer, and obesity. Thus, the circadian clock plays a crucial role in maintaining metabolic and digestive health.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Review
Endocrinology & Metabolism
Si-Ke He, Jia-Hao Wang, Tao Li, Shan Yin, Jian-Wei Cui, Yun-Fei Xiao, Yin Tang, Jia Wang, Yun-Jin Bai
Summary: This article reviews the relationship between circadian rhythm disturbance and kidney stone disease (KSD), summarizing the risk factors and treatment methods. The results indicate that KSD is associated with systemic disorders such as metabolic syndrome, inflammatory bowel disease, and microbiome dysbiosis, and some chronotherapies have been proven effective.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maria Savino, Claudio Carmine Guida, Maria Nardella, Emanuele Murgo, Bartolomeo Augello, Giuseppe Merla, Salvatore De Cosmo, Antonio Fernando Savino, Roberto Tarquini, Francesco Cei, Filippo Aucella, Gianluigi Mazzoccoli
Summary: This article investigates the relationship between heme biosynthesis disorders and altered expression of circadian genes, finding that changes in circadian gene expression may be associated with the symptoms and signs of porphyria patients.
Review
Cell Biology
Ya Niu, Shuang Tang
Summary: The circadian system plays a crucial role in regulating physiological functions and has been found to influence cancer risk and progression. Recent studies have shown that certain nuclear receptors, which regulate the circadian clock, also play important roles in multiple cancer processes.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Review
Plant Sciences
Alena Patnaik, Hemasundar Alavilli, Jnanendra Rath, Kishore C. S. Panigrahi, Madhusmita Panigrahy
Summary: Circadian clock components exhibit structural variations in different plant systems, and functional variations during various abiotic stresses. These variations are crucial for plant fitness and adaptation.
Article
Gastroenterology & Hepatology
Min Chen, Yanke Lin, Yongkang Dang, Yifei Xiao, Fugui Zhang, Guanghui Sun, Xuejun Jiang, Li Zhang, Jianhao Du, Shuyi Duan, Xiaojian Zhang, Zifei Qin, Jing Yang, Kaisheng Liu, Baojian Wu
Summary: This study reveals that the intestinal clock plays a crucial role in regulating liver rhythmicity and metabolism. The loss of the intestinal clock leads to a large-scale reprogramming of the liver transcriptome and alters hepatic metabolism. The intestinal clock controls the rhythmicity of the hepatic transcription factor SREBP-1c, which further affects hepatic lipogenesis and gluconeogenesis. These findings suggest that targeting intestinal rhythms may be a new approach for improving metabolic health.
JOURNAL OF HEPATOLOGY
(2023)
Article
Biology
Suil Kim, Douglas G. McMahon
Summary: This study reveals that light input to the SCN can change the waveform of molecular clockworks, marking clock advances and delays at simulated dawn and dusk. The changes in waveform seem to be greatest in the ventrolateral SCN, while the effects on period are greatest in the dorsomedial SCN, suggesting spatiotemporally distinct responses within the SCN neural network.
Article
Biochemical Research Methods
Shin-Ichi Koda, Shinji Saito
Summary: The formation of the clock protein complex in cyanobacteria relies on the slow KaiB-KaiC interaction, which is promoted by inhibiting ADP/ATP exchange through accumulating ADP molecules. This inhibition not only accelerates complex formation, but also contributes to period robustness under environmental perturbations. Moreover, the stabilization of the binding-competent C1 by KaiB binding and relatively fast ADP/ATP exchange in the binding-incompetent C1 are essential for this simultaneous promotion and acceleration.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Gary K. Chow, Archana G. Chavan, Joel C. Heisler, Yong-Gang Chang, Andy LiWang, R. David Britt
Article
Biochemistry & Molecular Biology
Lu Hong, Danylo O. Lavrentovich, Archana Chavan, Eugene Leypunskiy, Eileen Li, Charles Matthews, Andy LiWang, Michael J. Rust, Aaron R. Dinner
MOLECULAR SYSTEMS BIOLOGY
(2020)
Article
Microbiology
Yevgeni Yegorov, Eleonora Sendersky, Shaul Zilberman, Elad Nagar, Hiba Waldman Ben-Asher, Eyal Shimoni, Ryan Simkovsky, Susan S. Golden, Andy LiWang, Rakefet Schwarz
Summary: This study identifies novel components of cyanobacterial biofilm regulation and suggests that cyanobacteria may use the same complex for the assembly of motility appendages and protein secretion. This broadens the understanding of pilus assembly/secretion in diverse bacteria and aims to control the formation of cyanobacterial biofilms.
Article
Biochemistry & Molecular Biology
Madhurima Das, Nanhao Chen, Andy LiWang, Lee-Ping Wang
Summary: Metamorphic proteins are able to switch between different folds under native conditions. Uncovering the metamorphome requires computational screening and experimental validation. Understanding the properties of these proteins could lead to novel applications as sensors.
Editorial Material
Biochemistry & Molecular Biology
Patricia J. LiWang, Lee-Ping Wang, Andy LiWang
Summary: The study reveals that the ancestors of XCL1 developed metamorphic properties about 150 million years ago, and these properties are believed to be adaptive. The zigzagging evolutionary path also unveils three design principles that can be applied in technological applications.
TRENDS IN BIOCHEMICAL SCIENCES
(2021)
Editorial Material
Biochemistry & Molecular Biology
Andy LiWang, Lauren L. Porter, Lee-Ping Wang
Article
Chemistry, Multidisciplinary
Gary K. Chow, Archana G. Chavan, Joel Heisler, Yong-Gang Chang, Ning Zhang, Andy LiWang, R. David Britt
Summary: In this study, the authors used EPR spectroscopy to identify and quantify two subpopulations of KaiC-bound KaiB, providing kinetic evidence for their intermediacy as bridges and nucleation sites. Furthermore, they showed that the relative abundance of these subpopulations is dependent on the phosphorylation state of KaiC and the presence of KaiA. Finally, the authors demonstrated that the interconversion between these subpopulations is linked to the phosphorylation cycle of KaiC.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Yuanpeng Janet Huang, Ning Zhang, Beate Bersch, Krzysztof Fidelis, Masayori Inouye, Yojiro Ishida, Andriy Kryshtafovych, Naohiro Kobayashi, Yutaka Kuroda, Gaohua Liu, Andy LiWang, G. V. T. Swapna, Nan Wu, Toshio Yamazaki, Gaetano T. Montelione
Summary: NMR studies provide unique information on protein conformations in solution, with CASP14 showing varying prediction results for targets with NMR-based structures. By comparing prediction models and experimental NMR data, new methods were explored for guiding NMR data analysis.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2021)
Article
Multidisciplinary Sciences
Archana G. Chavan, Jeffrey A. Swan, Joel Heisler, Cigdem Sancar, Dustin C. Ernst, Mingxu Fang, Joseph G. Palacios, Rebecca K. Spangler, Clive R. Bagshaw, Sarvind Tripathi, Priya Crosby, Susan S. Golden, Carrie L. Partch, Andy LiWang
Summary: The study successfully reconstructed a complete cyanobacterial circadian clock system in vitro, including the central oscillator, signal transduction pathways, downstream transcription factor, and promoter DNA. By monitoring the oscillations in real time with a fluorescence-based readout, the study revealed previously unknown mechanisms by which the circadian system of cyanobacteria maintains pace and rhythmicity under variable protein concentrations.
Article
Biochemistry & Molecular Biology
Jeffrey A. Swan, Colby R. Sandate, Archana G. Chavan, Alfred M. Freeberg, Diana Etwaru, Dustin C. Ernst, Joseph G. Palacios, Susan S. Golden, Andy LiWang, Gabriel C. Lander, Carrie L. Partch
Summary: This work uncovers the mechanism of phosphorylation-dependent day/night signaling by KaiC in the cyanobacterial circadian clock. Cryogenic-electron microscopy analysis reveals that the C-terminal domain of KaiC undergoes structural changes, causing destabilization during the day and rigidification at night, leading to the binding of clock proteins and regulation of circadian rhythms. The phosphorylation-dependent KaiB association is coupled to ATPase activity, providing insights into the overall regulation of cyanobacterial circadian rhythms.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Mingxu Fang, Archana G. Chavan, Andy LiWang, Susan S. Golden
Summary: In this study, the researchers used the IVC reactions and massively parallel experiments to study entrainment, the synchronization of the circadian clock with the environment. The results showed that the IVC better explains the in vivo clock-resetting phenotypes of wild-type and mutant strains, and the output components are deeply engaged with the core oscillator, affecting the way input signals entrain the core pacemaker. These findings blur the line between input and output pathways and support the previous demonstration that key output components are fundamental parts of the clock.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Archana Chavan, Joel Heisler, Yong-Gang Chang, Susan S. Golden, Carrie L. Partch, Andy LiWang
Summary: Circadian clocks, which regulate metabolic processes based on local time, are important for the health of diverse life forms. However, studying their mechanisms in vivo is challenging. Recent research has successfully reconstituted the circadian clock of cyanobacteria in vitro, allowing real-time observation of clock proteins and DNA under controlled conditions. This breakthrough provides protocols for other labs to investigate how changing environments impact the core oscillator and transcriptional regulation.
Meeting Abstract
Biophysics
Andy LiWang, Archana G. Chavan, Jeffrey A. Swan, Joel C. Heisler, Cigdem Sancar, Dustin Ernst, Mingxu Fang, Clive R. Bagshaw, Sarvind Tripathi, Priya Crosby, Susan S. Golden, Carrie L. Partch
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Alfred M. Freeberg, Jeffrey A. Swan, Colby Sandate, Archana G. Chavan, Dustin Ernst, Diana Etwaru, Joseph G. Palacios, Susan Golden, Andy LiWang, Gabriel C. Lander, Carrie L. Partch
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Jeffrey A. Swan, Colby R. Sandate, Alfred M. Freeberg, Joel C. Heisler, Diana L. Etwaru, Cigdem Sancar, Dustin C. Ernst, Joseph G. Palacios, Clive R. Bagshaw, Archana G. Chavan, Susan S. Golden, Andy LiWang, Gabriel C. Lander, Carrie L. Partch
BIOPHYSICAL JOURNAL
(2022)