Research On Temperature Regulation Gating Mechanism Of TRPM8 Channel

TRPM8 channel is a subtype of TRP(Transient Receptor Potential)superfamily and widely exists in cell membrane or organelle membrane.It plays an important role in regulating cell growth,apoptosis,proliferation and physiological functions.It is a non-selective cation channel that is regulated by a variety of physical and chemical factors such as PIP2,eucalyptol,and so on,but cold stimulation,menthol and borneol can specifically activate the TRPM8 channel.Studies have shown that due to the lack of TRPM8 channel protein crystal structure at present,its function and microscopic molecular mechanism is unclear.In view of the above reasons,the three-dimensional structure of mouse TRPM8 channel was constructed by means of homology modeling with the crystal structure of TRPV1 channel open state 3J5 Q and closed state 3J5 P as a template.Through molecular dynamics simulation,the three-dimensional structure of the model is optimized and the energy is minimized.The molecular mechanism of the conformation changes of the channel lower at different temperatures effected by interactions is mainly discussed.The conclusions reached are as follows: 1.Successful establishment the open and closed state of mouse TRPM8 channel;2.Low temperature is conducive to maintaining the opening of the channel lower gate and clearly defined generation and transmission of the interaction force;3.The method of molecular docking was also adopted in this paper.With the use of TRPM8 as acceptor and menthol and borneol as ligands,the mechanism of ligand regulation channel was revealed to further verify the reliability of our constructed structure.In this paper,the TRPM8 channel was taken as the research object,and the above valuable results were obtained through the study of the lower gate molecular mechanism under the temperature regulation channel.These works are of great significance for revealing the temperature regulation of the TRPM8 channel and other family members' structural functions.It also provides theoretical support and ideas for the molecular design and synthesis of targeted drugs targeting TRPM8 channels.