A Slow Conformational Switch in the BMAL1 Transactivation Domain Modulates Circadian Rhythms

Molecular Cell
Chelsea L GustafsonCarrie L Partch

Abstract

The C-terminal transactivation domain (TAD) of BMAL1 (brain and muscle ARNT-like 1) is a regulatory hub for transcriptional coactivators and repressors that compete for binding and, consequently, contributes to period determination of the mammalian circadian clock. Here, we report the discovery of two distinct conformational states that slowly exchange within the dynamic TAD to control timing. This binary switch results from cis/trans isomerization about a highly conserved Trp-Pro imide bond in a region of the TAD that is required for normal circadian timekeeping. Both cis and trans isomers interact with transcriptional regulators, suggesting that isomerization could serve a role in assembling regulatory complexes in vivo. Toward this end, we show that locking the switch into the trans isomer leads to shortened circadian periods. Furthermore, isomerization is regulated by the cyclophilin family of peptidyl-prolyl isomerases, highlighting the potential for regulation of BMAL1 protein dynamics in period determination.

Associated Datasets

Apr 13, 2017·Carrie Partch, Chelsea Gustafson
Apr 13, 2017·Chelsea Gustafson, Carrie Partch
Apr 13, 2017·Carrie Partch, Chelsea Gustafson
Apr 13, 2017·Carrie Partch, Chelsea Gustafson
Apr 13, 2017·Chelsea Gustafson, Carrie Partch
Apr 13, 2017·Carrie Partch, Chelsea Gustafson
Apr 13, 2017·Carrie Partch, Chelsea Gustafson
Apr 13, 2017·Carrie Partch, Chelsea Gustafson
Apr 13, 2017·Chelsea Gustafson, Carrie Partch
Apr 13, 2017·Carrie Partch, Chelsea Gustafson
Apr 13, 2017·Carrie Partch, Chelsea Gustafson
Apr 13, 2017·Chelsea Gustafson, Carrie Partch
Apr 13, 2017·Carrie Partch, Chelsea Gustafson
Apr 13, 2017·Carrie Partch, Chelsea Gustafson
Apr 13, 2017·Chelsea Gustafson, Carrie Partch

Citations

Oct 19, 2017·Cold Spring Harbor Perspectives in Biology·Koji L Ode, Hiroki R Ueda
Nov 8, 2018·The European Journal of Neuroscience·Clark Rosensweig, Carla B Green
Dec 7, 2018·Biomolecules·Caroline Rajiv, Tara L Davis
Jun 21, 2017·Nature Chemical Biology·Grant Miura
Sep 25, 2017·The Biochemical Journal·Caroline RajivTara L Davis
Nov 21, 2019·Cell Proliferation·Shaoling YuLili Chen
Jun 9, 2019·Nature Communications·Dailu ChenLukasz A Joachimiak
Jul 3, 2020·Frontiers in Molecular Biosciences·Katrine BuggeBirthe B Kragelund
Aug 24, 2017·Proceedings of the National Academy of Sciences of the United States of America·Ying ZhangChristine Merlin
Aug 22, 2018·Nature Communications·Franziska ZoselBenjamin Schuler
Nov 10, 2018·Nature Communications·Richard BrustDouglas J Kojetin
Nov 27, 2020·Emerging Topics in Life Sciences·Fa-An Chao, R Andrew Byrd
Oct 28, 2020·Proceedings of the National Academy of Sciences of the United States of America·Gian Carlo G ParicoCarrie L Partch
Nov 13, 2020·Cell Communication and Signaling : CCS·Jacqueline F PelhamJennifer M Hurley
Oct 31, 2020·BMC Biology·Snehajyoti ChatterjeeTed Abel
Jan 17, 2020·Journal of Molecular Biology·Carrie L Partch
Apr 4, 2021·International Journal of Molecular Sciences·Marta Kolonko-AdamskaBeata Greb-Markiewicz
Oct 20, 2019·Current Opinion in Structural Biology·Aaron H Phillips, Richard W Kriwacki
May 3, 2021·Seminars in Cell & Developmental Biology·Jonathan M PhilpottCarrie L Partch
Jun 20, 2021·Nature Communications·Christian H GabrielAchim Kramer

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.