title: The structure of a conserved piezo channel domain reveals a topologically distinct β sandwich fold.
abstract: Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2,000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a topologically distinct β sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in dehydrated hereditary stomatocytosis patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be-identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels.
authors.affiliation: Biochemistry and Molecular Biophysics Graduate Option, California Institute of Technology, Pasadena, CA 91125, USA; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Aron
authors.initials: A
authors.lastname: Kamajaya
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Jens T
authors.initials: JT
authors.lastname: Kaiser
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Jonas
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Reid
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: dcrees@caltech.edu.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Rees
mesh_terms: D000137:Acid-Base Imbalance / Q000235:genetics; D000595:Amino Acid Sequence; D000745:Anemia, Hemolytic, Congenital / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000378:metabolism; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics; D004913:Erythrocytes, Abnormal; D006801:Humans; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008661:Metabolism, Inborn Errors / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D007473:Ion Channels; C515204:PIEZO1 protein, human; C571430:Piezo protein, Drosophila; C552920:Piezo1 protein, mouse; C552921:Piezo2 protein, mouse