cryo-em structure of TRPM4 reveals a calcium binding site
Henriette’s postdoctoral research at UCSF led to the first high-resolution structures of the human transient receptor potential (TRP) melastatin subtype 4 (hTRPM4) ion channel, a protein important in cardiac physiology. The team determined two structures of hTRPM4 using single particle cryo–EM, identifying a hitherto unassigned calcium-binding site in hTRPM4 and the first divalent cation binding site in a TRP channel. Since publishing the hTRPM4 structures, the same ion binding site was found in several other TRP channels, making our discovery relevant for the entire TRP ion channel field. The structures provide leads for how hTRPM4 and other calcium modulated TRP channels open in response to calcium and improve our understanding of the molecular mechanisms underlying cardiovascular physiology and diseases and how these may be pharmacologically modulated.
References
Structure of the human TRPM4 ion channel in a lipid nanodisc
Autzen HE, Myasnikov AG, Campbell MG, Asarnow D, Julius D, Cheng Y
Science, 2018, 359 (6372), pp 228-232.
PDB: 6BQR, 6BQV
EMDB: EMD-7132, EMD-7133