title: A synthetic prestin reveals protein domains and molecular operation of outer hair cell piezoelectricity.
abstract: Prestin, a transporter-like protein of the SLC26A family, acts as a piezoelectric transducer that mediates the fast electromotility of outer hair cells required for cochlear amplification and auditory acuity in mammals. Non-mammalian prestin orthologues are anion transporters without piezoelectric activity. Here, we generated synthetic prestin (SynPres), a chimera of mammalian and non-mammalian prestin exhibiting both, piezoelectric properties and anion transport. SynPres delineates two distinct domains in the protein's transmembrane core that are necessary and sufficient for generating electromotility and associated non-linear charge movement (NLC). Functional analysis of SynPres showed that the amplitude of NLC and hence electromotility are determined by the transport of monovalent anions. Thus, prestin-mediated electromotility is a dual-step process: transport of anions by an alternate access cycle, followed by an anion-dependent transition generating electromotility. The findings define structural and functional determinants of prestin's piezoelectric activity and indicate that the electromechanical process evolved from the ancestral transport mechanism.
authors.affiliation: Institute of Physiology, University of Freiburg, Freiburg, Germany.
authors.forename: Thorsten J
authors.initials: TJ
authors.lastname: Schaechinger
authors.forename: Dmitry
authors.initials: D
authors.lastname: Gorbunov
authors.forename: Christian R
authors.initials: CR
authors.lastname: Halaszovich
authors.forename: Tobias
authors.initials: T
authors.lastname: Moser
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kügler
authors.forename: Bernd
authors.initials: B
authors.lastname: Fakler
authors.forename: Dominik
authors.initials: D
authors.lastname: Oliver
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000838:Anions / Q000378:metabolism; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement; D006224:Cricetinae; D003412:Cricetulus; D025802:Electric Capacitance; D004594:Electrophysiology; D018072:Hair Cells, Auditory, Outer / Q000502:physiology*; D017136:Ion Transport; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000502:physiology*; D009924:Organ Culture Techniques; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000076988:Sulfate Transporters; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D027321:Anion Transport Proteins; D000838:Anions; D020409:Molecular Motor Proteins; C498720:Pres protein, mouse; D011993:Recombinant Fusion Proteins; C409207:Slc26a5 protein, rat; D000076988:Sulfate Transporters; D029961:Zebrafish Proteins