6DRK
Structure of TRPM2 ion channel receptor by single particle electron cryo-microscopy, Apo state
Summary for 6DRK
| Entry DOI | 10.2210/pdb6drk/pdb |
| EMDB information | 7999 8901 |
| Descriptor | Transient receptor potential cation channel, subfamily M, member 2 (1 entity in total) |
| Functional Keywords | transport protein |
| Biological source | Danio rerio (Zebrafish) |
| Total number of polymer chains | 4 |
| Total formula weight | 674923.19 |
| Authors | Du, J.,Lu, W.,Huang, Y.,Winkler, P.,Sun, W. (deposition date: 2018-06-12, release date: 2018-09-19, Last modification date: 2025-05-14) |
| Primary citation | Huang, Y.,Winkler, P.A.,Sun, W.,Lu, W.,Du, J. Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium. Nature, 562:145-149, 2018 Cited by PubMed Abstract: Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable, non-selective cation channel that has an essential role in diverse physiological processes such as core body temperature regulation, immune response and apoptosis. TRPM2 is polymodal and can be activated by a wide range of stimuli, including temperature, oxidative stress and NAD-related metabolites such as ADP-ribose (ADPR). Its activation results in both Ca entry across the plasma membrane and Ca release from lysosomes, and has been linked to diseases such as ischaemia-reperfusion injury, bipolar disorder and Alzheimer's disease. Here we report the cryo-electron microscopy structures of the zebrafish TRPM2 in the apo resting (closed) state and in the ADPR/Ca-bound active (open) state, in which the characteristic NUDT9-H domains hang underneath the MHR1/2 domain. We identify an ADPR-binding site located in the bi-lobed structure of the MHR1/2 domain. Our results provide an insight into the mechanism of activation of the TRPM channel family and define a framework for the development of therapeutic agents to treat neurodegenerative diseases and temperature-related pathological conditions. PubMed: 30250252DOI: 10.1038/s41586-018-0558-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.8 Å) |
Structure validation
Download full validation report
