A folding reaction at the C-terminal domain drives temperature sensing in TRPM8 channels
| Autor: | Karen Castillo, Fernando D. González-Nilo, Ramon Latorre, Ignacio Diaz-Franulic, Natalia Raddatz |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Protein Folding Protein Conformation TRPM Cation Channels Gating Xenopus laevis Transient receptor potential channel Protein Domains TRPM8 Animals Humans Coiled coil Multidisciplinary Chemistry C-terminus Cryoelectron Microscopy Biological Sciences Cold Temperature Mutation Mutagenesis Site-Directed Oocytes Biophysics Thermodynamics Protein folding CTD Ion Channel Gating Communication channel |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2004303117 |
| Popis: | In mammals, temperature-sensitive TRP channels make membrane conductance of cells extremely temperature dependent, allowing the detection of temperature ranging from noxious cold to noxious heat. We progressively deleted the distal carboxyl terminus domain (CTD) of the cold-activated melastatin receptor channel, TRPM8. We found that the enthalpy change associated with channel gating is proportional to the length of the CTD. Deletion of the last 36 amino acids of the CTD transforms TRPM8 into a reduced temperature-sensitivity channel (Q(10) ∼4). Exposing the intracellular domain to a denaturing agent increases the energy required to open the channel indicating that cold drives channel gating by stabilizing the folded state of the CTD. Experiments in the presence of an osmoticant agent suggest that channel gating involves a change in solute-inaccessible volume in the CTD of ∼1,900 Å(3). This volume matches the void space inside the coiled coil according to the cryogenic electron microscopy structure of TRPM8. The results indicate that a folding–unfolding reaction of a specialized temperature-sensitive structure is coupled to TRPM8 gating. |
| Databáze: | OpenAIRE |
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