Year: 2019
Type: article
Abstract: The transient receptor potential melastatin 2 (TRPM2) channel plays a key role in redox sensation in many cell types. Channel activation requires binding of both ADP-ribose (ADPR) and Ca 2+ . The recently published TRPM2 structures from Danio rerio in the ligand-free and the ADPR/Ca 2+ -bound conditions represent the channel in closed and open states, which uncovered substantial tertiary and quaternary conformational rearrangements. However, it is unclear how these rearrangements are achieved within the tetrameric channel during channel gating. Here we report the cryo-electron microscopy structures of Danio rerio TRPM2 in the absence of ligands, in complex with Ca 2+ alone, and with both ADPR and Ca 2+ , resolved to ~4.3 Å, ~3.8 Å, and ~4.2 Å, respectively. In contrast to the published results, our studies capture ligand-bound TRPM2 structures in two-fold symmetric intermediate states, offering a glimpse of the structural transitions that bridge the closed and open conformations.
Source: Nature Communications
Language: English
Topic: Ion Channels and Receptors
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: National Science Foundation, U.S. Department of Health and Human Services, Pew Charitable Trusts, Amgen, Thailand Science Research and Innovation, National Institutes of Health, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Biomedical Imaging and Bioengineering
Awards: G1092267351, Structure, function, and pharmacology of neuronal membrane transport proteins, Conformational ensembles associated with TRPV3 gating, G3144446506, G3315282585, G3609795425, Molecular basis of axonal transport described by high-resolution 3D imaging, G700478798, G7212041399, G7341544827, COMPUTING AND DATA STORAGE CLUSTER FOR ELECTRON MICROSCOPY, G9000017079, G9000070529, NIEHS Cryo-EM Core Facility, G92184435
OpenAlex ID: W2969779171