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Open AccessArticle

TRPM6 N-Terminal CaM- and S100A1-Binding Domains

Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo namesti 2, 160 00 Prague 6, Czech Republic
Second Faculty of Medicine, Charles University, V Uvalu 84, 150 06 Prague 5, Czech Republic
Faculty of Mathematics and Physics, Charles University, Ke Karlovu 5, 121 16 Prague 2, Czech Republic
Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(18), 4430;
Received: 30 July 2019 / Revised: 2 September 2019 / Accepted: 4 September 2019 / Published: 9 September 2019
(This article belongs to the Collection Feature Papers in Molecular Biophysics)
Transient receptor potential (TRPs) channels are crucial downstream targets of calcium signalling cascades. They can be modulated either by calcium itself and/or by calcium-binding proteins (CBPs). Intracellular messengers usually interact with binding domains present at the most variable TRP regions—N- and C-cytoplasmic termini. Calmodulin (CaM) is a calcium-dependent cytosolic protein serving as a modulator of most transmembrane receptors. Although CaM-binding domains are widespread within intracellular parts of TRPs, no such binding domain has been characterised at the TRP melastatin member—the transient receptor potential melastatin 6 (TRPM6) channel. Another CBP, the S100 calcium-binding protein A1 (S100A1), is also known for its modulatory activities towards receptors. S100A1 commonly shares a CaM-binding domain. Here, we present the first identified CaM and S100A1 binding sites at the N-terminal of TRPM6. We have confirmed the L520-R535 N-terminal TRPM6 domain as a shared binding site for CaM and S100A1 using biophysical and molecular modelling methods. A specific domain of basic amino acid residues (R526/R531/K532/R535) present at this TRPM6 domain has been identified as crucial to maintain non-covalent interactions with the ligands. Our data unambiguously confirm that CaM and S100A1 share the same binding domain at the TRPM6 N-terminus although the ligand-binding mechanism is different. View Full-Text
Keywords: TRPM6; calmodulin binding motif; binding domain; CaM and S100A1; fluorescence anisotropy; molecular modelling TRPM6; calmodulin binding motif; binding domain; CaM and S100A1; fluorescence anisotropy; molecular modelling
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Zouharova, M.; Herman, P.; Hofbauerová, K.; Vondrasek, J.; Bousova, K. TRPM6 N-Terminal CaM- and S100A1-Binding Domains. Int. J. Mol. Sci. 2019, 20, 4430.

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