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Particle stack from TRPM8 bound to calcium dataset


ABSTRACT:

SUBMITTER: Yifan Cheng 

PROVIDER: EMPIAR-11233 | biostudies-other |

REPOSITORIES: biostudies-other

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Publications

Structural insights into TRPM8 inhibition and desensitization.

Diver Melinda M MM   Cheng Yifan Y   Julius David D  

Science (New York, N.Y.) 20190905 6460


The transient receptor potential melastatin 8 (TRPM8) ion channel is the primary detector of environmental cold and an important target for treating pathological cold hypersensitivity. Here, we present cryo-electron microscopy structures of TRPM8 in ligand-free, antagonist-bound, or calcium-bound forms, revealing how robust conformational changes give rise to two nonconducting states, closed and desensitized. We describe a malleable ligand-binding pocket that accommodates drugs of diverse chemic  ...[more]

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