Abstract
The TRPM (transient receptor potential melastatin) family belongs to the superfamily of TRP cation channels. The TRPM subfamily is composed of eight members that are involved in diverse biological functions such as temperature sensing, inflammation, insulin secretion, and redox sensing. Since the first cloning of TRPM1 in 1998, tremendous progress has been made uncovering the function, structure, and pharmacology of this family. Complete structures of TRPM2, TRPM4, and TRPM8, as well as a partial structure of TRPM7, have been determined by cryo-EM, providing insights into their channel assembly, ion permeation, gating mechanisms, and structural pharmacology. Here we summarize the current knowledge about channel structure, emphasizing general features and principles of the structure of TRPM channels discovered since 2017. We also discuss some of the key unresolved issues in the field, including the molecular mechanisms underlying voltage and temperature dependence, as well as the functions of the TRPM channels' C-terminal domains.
🔬 Techniques
🔭 Microscopes
🧬 Organisms
✨ Fluorophores
🧪 Sample Preparation
🏭 Microscope Brands
💾 Data Repositories
🏛️ Research Organizations (ROR)
Affiliated research institutions:
📊 Figures
Figure 1:
Family tree and domain organization of TRPM family.
a, Domain organization of a monomer of the human TRPM family; the C-terminal domain (CTD) differs among family members. The colors of TMD refer to Figure 6 . b, The relatedness of the human TRPM famil...
Figure 2:
Comparison of the tetrameric architecture and single subunits of representative TRPM channels.
a-d , Overall structures of ( a ) hs TRPM2, ( b ) hs TRPM4, ( c ) mm TRPM7, and ( d ) fa TRPM8 viewed parallel to the membrane. The mm TRPM7 structure is not full length; the kinase domain is truncate...
Figure 3:
Ligand-binding sites of hs TRPM2, hs TRPM4, and fa TRPM8.
The locations of available ligand-binding sites are boxed. Ca 2+ is shown as black spheres, while other ligands and key residues involved in ligand binding are shown as sticks. The binding site of Ca ...
Figure 4:
Comparison of ion-conducting pores.
The shape and size of the ion-conducting pore of ( a ) EDTA- dr TRPM2, ( b ) ADPR/Ca 2+ - dr TRPM2, ( c ) Ca 2+ - nv TRPM2, ( d ) Ca 2+ /DVT- hs TRPM4, and ( e ) mm TRPM7 (not full length). The side c...
Figure 5:
Gating mechanism of the voltage-independent TRPM2 channel.
Structures of the ( a) EDTA- dr TRPM2 and ( b ) ADPR/Ca 2+ - dr TRPM2. Comparison of the ( c ) NUDT9-H domains and the ( d ) MHR1/2 domains of EDTA- hs TRPM2 and ADPR/Ca 2+ - hs TRPM2 by superimpositi...
Figure 6:
Schematic of ligand sensing and the activation mechanism of TRPM2.
Conformational changes of TRPM2 upon ligand binding are shown by arrows. 8-Br-cADPR binds only to the MHR1/2 domain and inhibits the TRPM2 channel by stabilizing the MHR1/2 domain in apo-like conforma...
Figure images are served from the NIH/NLM PubMed Central Open Access Subset or Europe PMC; copyright remains with the publishers and authors.
💬 Discussion
0 commentsNo comments yet. Be the first to start a discussion!
Leave a Comment