TRPM7 N-terminal region forms complexes with calcium binding proteins CaM and S100A1
Kristyna Bousova,
Monika Zouharova,
Petr Herman,
Veronika Vetyskova,
Katerina Jiraskova,
Jiri Vondrasek
Affiliations
Kristyna Bousova
Department of Bioinformatics, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo namesti 2, 16000 Prague, Czech Republic; Corresponding author.
Monika Zouharova
Department of Bioinformatics, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo namesti 2, 16000 Prague, Czech Republic; Department of Biochemistry and Patobiochemistry, Second Faculty of Medicine, Charles University, 150 06 Prague 5, V Uvalu 84, Czech Republic
Petr Herman
Department Faculty of Mathematics and Physics, Charles University, Ke Karlovu 5, 12116 Prague, Czech Republic
Veronika Vetyskova
Department of Bioinformatics, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo namesti 2, 16000 Prague, Czech Republic; Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technicka 5, 166 28 Prague, Czech Republic
Katerina Jiraskova
Department of Bioinformatics, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo namesti 2, 16000 Prague, Czech Republic
Jiri Vondrasek
Department of Bioinformatics, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo namesti 2, 16000 Prague, Czech Republic
Transient receptor potential melastatin 7 (TRPM7) represents melastatin TRP channel with two significant functions, cation permeability and kinase activity. TRPM7 is widely expressed among tissues and is therefore involved in a variety of cellular functions representing mainly Mg2+ homeostasis, cellular Ca2+ flickering, and the regulation of DNA transcription by a cleaved kinase domain translocated to the nucleus. TRPM7 participates in several important biological processes in the nervous and cardiovascular systems. Together with the necessary function of the TRPM7 in these tissues and its recently analyzed overall structure, this channel requires further studies leading to the development of potential therapeutic targets. Here we present the first study investigating the N-termini of TRPM7 with binding regions for important intracellular modulators calmodulin (CaM) and calcium-binding protein S1 (S100A1) using in vitro and in silico approaches. Molecular simulations of the discovered complexes reveal their potential binding interfaces with common interaction patterns and the important role of basic residues present in the N-terminal binding region of TRPM.
