Casein kinase 1 dynamics underlie substrate selectivity and the PER2 circadian phosphoswitch.
human
human cell culture
in vitro biochemistry
molecular biophysics
mouse
mouse cell culture
protiens
structural biology
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
11 02 2020
11 02 2020
Historique:
received:
03
10
2019
accepted:
25
01
2020
entrez:
12
2
2020
pubmed:
12
2
2020
medline:
7
4
2021
Statut:
epublish
Résumé
Post-translational control of PERIOD stability by Casein Kinase 1δ and ε (CK1) plays a key regulatory role in metazoan circadian rhythms. Despite the deep evolutionary conservation of CK1 in eukaryotes, little is known about its regulation and the factors that influence substrate selectivity on functionally antagonistic sites in PERIOD that directly control circadian period. Here we describe a molecular switch involving a highly conserved anion binding site in CK1. This switch controls conformation of the kinase activation loop and determines which sites on mammalian PER2 are preferentially phosphorylated, thereby directly regulating PER2 stability. Integrated experimental and computational studies shed light on the allosteric linkage between two anion binding sites that dynamically regulate kinase activity. We show that period-altering kinase mutations from humans to
Identifiants
pubmed: 32043967
doi: 10.7554/eLife.52343
pii: 52343
pmc: PMC7012598
doi:
pii:
Substances chimiques
PER2 protein, human
0
Period Circadian Proteins
0
Casein Kinase I
EC 2.7.11.1
Banques de données
PDB
['6PXO', '6PXN', '6PXP']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : OD018455
Pays : United States
Organisme : NIH HHS
ID : GM107069
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM107069
Pays : United States
Organisme : NIH HHS
ID : S10 OD018455
Pays : United States
Organisme : NIGMS NIH HHS
ID : R25 GM058903
Pays : United States
Organisme : NIH HHS
ID : GM133149
Pays : United States
Organisme : NIH HHS
ID : GM031749
Pays : United States
Organisme : NIH HHS
ID : GM121507
Pays : United States
Informations de copyright
© 2020, Philpott et al.
Déclaration de conflit d'intérêts
JP, RN, CR, AF, SH, LY, RP, ST, DV, CP No competing interests declared
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