Backbone resonance assignments of the catalytic and regulatory domains of Ca 2+ /calmodulin-dependent protein kinase 1D
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ARTICLE
Backbone resonance assignments of the catalytic and regulatory domains of Ca2+/calmodulin‑dependent protein kinase 1D Michael H. G. Tong1 · Mark Jeeves1 · Sundaresan Rajesh1 · Christian Ludwig1 · Marc Lenoir1 · Jitendra Kumar6 · Darren M. McClelland1 · Fedor Berditchevski1 · Julia A. Hubbard2 · Colin Kenyon3 · Sam Butterworth4 · Stefan Knapp5 · Michael Overduin6 Received: 12 February 2020 / Accepted: 21 May 2020 © The Author(s) 2020
Abstract The CaMK subfamily of Ser/Thr kinases are regulated by calmodulin interactions with their C-terminal regions. They are exemplified by Ca2+/calmodulin dependent protein kinase 1δ which is known as CaMK1D, CaMKIδ or CKLiK. CaMK1D mediates intracellular signalling downstream of C a2+ influx and thereby exhibits amplifications of Ca2+signals and polymorphisms that have been implicated in breast cancer and diabetes. Here we report the backbone 1H, 13C, 15N assignments of the 38 kDa human CaMK1D protein in its free state, including both the canonical bi-lobed kinase fold as well as the autoinhibitory and calmodulin binding domains. Keywords Protein resonance assignment · NMR · Calcium/calmodulin dependent protein kinase · CaMK1D · CaMKIδ · CKLiK
Biological context Protein kinases are important mediators of signal transduction, with approximately a 30% of all human proteins being phosphorylated (Cohen 2001). Their deregulation contributes to cancer and many other diseases, and is a major * Michael Overduin [email protected] 1
Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
2
Computational, Analytical and Structural Sciences, GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK
3
Faculty of Medicine and Health Sciences, Stellenbosch University, Francie Van Zijl Dr, Parow, Cape Town 7505, South Africa
4
Division of Pharmacy and Optometry, School of Health Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester M13 9PL, UK
5
Structural Genomics Consortium and Buchmann Institute for Molecular Life Sciences, Institute for Pharmaceutical Chemistry, Johann Wolfgang Goethe-University, Max‑von‑Laue‑Straße 9, 60438 Frankfurt am Main, Germany
6
Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada
focus of drug discovery efforts (Marsden and Knapp 2008). To date, 518 members have been identified in the human kinome, and are grouped into 10 sub families (Manning et al. 2002). Those that belong to calmodulin dependent kinases (CaMK) group share a similar domain organization. All are activated by binding of C a2+/calmodulin to their C-terminal regulatory region, releasing the catalytic domains to phosphorylate Ser/Thr residues in protein substrates to alter their functionality (Hook and Means 2001; Soderling and Stull 2001). No resonance assignments for any CaMK member have been reported, limiting analysis of their solution structures and interactions. The structure of CaMK1D consists of various functional modules
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