Structural insight into TRPV5 channel function and modulation
pmid: 30975749
pmc: PMC6500171
Structural insight into TRPV5 channel function and modulation
TRPV5 (transient receptor potential vanilloid 5) is a unique calcium-selective TRP channel essential for calcium homeostasis. Unlike other TRPV channels, TRPV5 and its close homolog, TRPV6, do not exhibit thermosensitivity or ligand-dependent activation but are constitutively open at physiological membrane potentials and modulated by calmodulin (CaM) in a calcium-dependent manner. Here we report high-resolution electron cryomicroscopy structures of truncated and full-length TRPV5 in lipid nanodiscs, as well as of a TRPV5 W583A mutant and TRPV5 in complex with CaM. These structures highlight the mechanism of calcium regulation and reveal a flexible stoichiometry of CaM binding to TRPV5.
- Hong Kong Polytechnic University China (People's Republic of)
- Hong Kong University of Science and Technology (香港科技大學) China (People's Republic of)
- Howard Hughes Medical Institute United States
- Radboud Institute for Molecular Life Sciences Netherlands
- STICHTING RADBOUD UNIVERSITEIT Netherlands
Models, Molecular, calmodulin, Protein Conformation, 1.1 Normal biological development and functioning, Medical Physiology, 610, Radboud University Medical Center, TRPV Cation Channels, Bioengineering, Chemical, Physiology - Radboud University Medical Center, Models, TRP channel, Nanotechnology, Animals, Cloning, Molecular, calcium, Biomedical and Clinical Sciences, Calcium Radioisotopes, Cryoelectron Microscopy, Molecular, Radboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life Sciences, Models, Chemical, Mutation, cryo-EM, Calcium, Generic health relevance, Rabbits, Cloning, Protein Binding
Models, Molecular, calmodulin, Protein Conformation, 1.1 Normal biological development and functioning, Medical Physiology, 610, Radboud University Medical Center, TRPV Cation Channels, Bioengineering, Chemical, Physiology - Radboud University Medical Center, Models, TRP channel, Nanotechnology, Animals, Cloning, Molecular, calcium, Biomedical and Clinical Sciences, Calcium Radioisotopes, Cryoelectron Microscopy, Molecular, Radboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life Sciences, Models, Chemical, Mutation, cryo-EM, Calcium, Generic health relevance, Rabbits, Cloning, Protein Binding
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