5X17

Crystal structure of murine CK1d in complex with ADP

Summary for 5X17

• Entry DOI: 10.2210/pdb5x17/pdb
• Related: 5X18
• Descriptor: Casein kinase I isoform delta, SULFATE ION, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: ck1d, kinase, transferase
• Biological source: Mus musculus (Mouse)
• Cellular location: Cytoplasm : Q9DC28
• Total number of polymer chains: 2
• Total formula weight: 70552.37

Authors

Kikuchi, M.,Shinohara, Y.,Ueda, H.R.,Umehara, T. (deposition date: 2017-01-25, release date: 2017-10-04, Last modification date: 2023-11-22)

Primary citation

Shinohara, Y.,Koyama, Y.M.,Ukai-Tadenuma, M.,Hirokawa, T.,Kikuchi, M.,Yamada, R.G.,Ukai, H.,Fujishima, H.,Umehara, T.,Tainaka, K.,Ueda, H.R.
Temperature-Sensitive Substrate and Product Binding Underlie Temperature-Compensated Phosphorylation in the Clock
Mol. Cell, 67:783-798.e20, 2017

PubMed Abstract: Temperature compensation is a striking feature of the circadian clock. Here we investigate biochemical mechanisms underlying temperature-compensated, CKIδ-dependent multi-site phosphorylation in mammals. We identify two mechanisms for temperature-insensitive phosphorylation at higher temperature: lower substrate affinity to CKIδ-ATP complex and higher product affinity to CKIδ-ADP complex. Inhibitor screening of ADP-dependent phosphatase activity of CKIδ identified aurintricarboxylic acid (ATA) as a temperature-sensitive kinase activator. Docking simulation of ATA and mutagenesis experiment revealed K224D/K224E mutations in CKIδ that impaired product binding and temperature-compensated primed phosphorylation. Importantly, K224D mutation shortens behavioral circadian rhythms and changes the temperature dependency of SCN's circadian period. Interestingly, temperature-compensated phosphorylation was evolutionary conserved in yeast. Molecular dynamics simulation and X-ray crystallography demonstrate that an evolutionally conserved CKI-specific domain around K224 can provide a structural basis for temperature-sensitive substrate and product binding. Surprisingly, this domain can confer temperature compensation on a temperature-sensitive TTBK1. These findings suggest the temperature-sensitive substrate- and product-binding mechanisms underlie temperature compensation.

PubMed: 28886336
DOI: 10.1016/j.molcel.2017.08.009

Experimental method

X-RAY DIFFRACTION (2 Å)