TRPM6 N-Terminal CaM- and S100A1-Binding Domains.

摘要: Transient receptor potential (TRPs) channels are crucial downstream targets of calcium signalling cascades. They can be modulated either by itself and/or 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 modulator transmembrane receptors. Although CaM-binding widespread within intracellular parts TRPs, no such domain has been characterised melastatin member—the transient 6 (TRPM6) channel. Another CBP, S100 A1 (S100A1), also known for its modulatory activities towards S100A1 commonly shares domain. Here, we first identified CaM sites N-terminal TRPM6. We have confirmed L520-R535 TRPM6 shared site using biophysical molecular modelling methods. A specific basic amino acid residues (R526/R531/K532/R535) this to maintain non-covalent interactions ligands. Our data unambiguously confirm that share same N-terminus although ligand-binding mechanism different.