title: The STAS domain of mammalian SLC26A5 prestin harbours an anion-binding site.
abstract: Prestin is a unique ATP- and Ca(2+)-independent molecular motor with piezoelectric characteristics responsible for the electromotile properties of mammalian cochlear outer hair cells, i.e. the capacity of these cells to modify their length in response to electric stimuli. This 'electromotility' is at the basis of the exceptional sensitivity and frequency selectivity distinctive of mammals. Prestin belongs to the SLC26 (solute carrier 26) family of anion transporters and needs anions to function properly, particularly Cl(-). In the present study, using X-ray crystallography we reveal that the STAS (sulfate transporter and anti-sigma factor antagonist) domain of mammalian prestin, considered an 'incomplete' transporter, harbours an unanticipated anion-binding site. In parallel, we present the first crystal structure of a prestin STAS domain from a non-mammalian vertebrate prestin (chicken) that behaves as a 'full' transporter. Notably, in chicken STAS, the anion-binding site is lacking because of a local structural rearrangement, indicating that the presence of the STAS anion-binding site is exclusive to mammalian prestin.
authors.affiliation: Department of Chemical Sciences, University of Padua, via Marzolo 1, 35131 Padua, Italy graziano.lolli@unipd.it roberto.battistutta@unipd.it.
authors.forename: Graziano
authors.initials: G
authors.lastname: Lolli
authors.affiliation: Department of Chemical Sciences, University of Padua, via Marzolo 1, 35131 Padua, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pasqualetto
authors.affiliation: Department of Chemical Sciences, University of Padua, via Marzolo 1, 35131 Padua, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Costanzi
authors.affiliation: Department of Chemical Sciences, University of Padua, via Marzolo 1, 35131 Padua, Italy.
authors.forename: Greta
authors.initials: G
authors.lastname: Bonetto
authors.affiliation: Department of Chemical Sciences, University of Padua, via Marzolo 1, 35131 Padua, Italy graziano.lolli@unipd.it roberto.battistutta@unipd.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Battistutta
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D027321:Anion Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000838:Anions; D001665:Binding Sites; D002645:Chickens; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D017386:Sequence Homology, Amino Acid; D000076988:Sulfate Transporters
chemical_list: D027321:Anion Transport Proteins; D000838:Anions; C409207:Slc26a5 protein, rat; D000076988:Sulfate Transporters
keywords: SLC26; STAS domain; anion transporters; crystal structure; electromotility; prestin