title: Piezo1 ion channel pore properties are dictated by C-terminal region.
abstract: Piezo1 and Piezo2 encode mechanically activated cation channels that function as mechanotransducers involved in vascular system development and touch sensing, respectively. Structural features of Piezos remain unknown. Mouse Piezo1 is bioinformatically predicted to have 30-40 transmembrane (TM) domains. Here, we find that nine of the putative inter-transmembrane regions are accessible from the extracellular side. We use chimeras between mPiezo1 and dPiezo to show that ion-permeation properties are conferred by C-terminal region. We further identify a glutamate residue within a conserved region adjacent to the last two putative TM domains of the protein, that when mutated, affects unitary conductance and ion selectivity, and modulates pore block. We propose that this amino acid is either in the pore or closely associates with the pore. Our results describe important structural motifs of this channel family and lay the groundwork for a mechanistic understanding of how Piezos are mechanically gated and conduct ions.
authors.affiliation: 1] Aix Marseille Université, CNRS, CRN2M-UMR7286, 13344 Marseille, France [2] Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coste
authors.affiliation: Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Swetha E
authors.initials: SE
authors.lastname: Murthy
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA.
authors.forename: Jayanti
authors.initials: J
authors.lastname: Mathur
authors.affiliation: Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Manuela
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Aix Marseille Université, CNRS, CRN2M-UMR7286, 13344 Marseille, France.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Mechioukhi
authors.affiliation: Aix Marseille Université, CNRS, CRN2M-UMR7286, 13344 Marseille, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Delmas
authors.affiliation: 1] Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, California 92037, USA [2] Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA.
authors.forename: Ardem
authors.initials: A
authors.lastname: Patapoutian
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data
chemical_list: D029721:Drosophila Proteins; D007473:Ion Channels; C571430:Piezo protein, Drosophila; C552920:Piezo1 protein, mouse; C552921:Piezo2 protein, mouse