TRPM6 N-Terminal CaM- and S100A1-Binding Domains

0510200 - ÚOCHB 2020 RIV CH eng J - Článek v odborném periodiku
Zouharová, Monika - Heřman, P. - Hofbauerová, Kateřina - Vondrášek, Jiří - Boušová, Kristýna
TRPM6 N-Terminal CaM- and S100A1-Binding Domains.
International Journal of Molecular Sciences. Roč. 20, č. 18 (2019), č. článku 4430. E-ISSN 1422-0067
Grant CEP: GA MŠMT(CZ) EF16_019/0000729
Institucionální podpora: RVO:61388963 ; RVO:61388971
Klíčová slova: TRPM6 * calmodulin binding motif * binding domain * CaM and S100A1 * fluorescence anisotropy * molecular modelling
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 4.556, rok: 2019
Způsob publikování: Open access
https://www.mdpi.com/1422-0067/20/18/4430

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.
Trvalý link: http://hdl.handle.net/11104/0300727