biostudies-literatureKuwabara MFMEXT | Japan Society for the Promotion of ScienceDeutscher Akademischer AustauschdienstDeutsche Forschungsgemeinschaft7145https://www.ebi.ac.uk/biostudies/studies/S-EPMC10628124biostudies-literatureUnknown14(1)The outstanding acuity of the mammalian ear relies on cochlear amplification, an active mechanism based on the electromotility (eM) of outer hair cells. eM is a piezoelectric mechanism generated by little-understood, voltage-induced conformational changes of the anion transporter homolog prestin (SLC26A5). We used a combination of molecular dynamics (MD) simulations and biophysical approaches to identify the structural dynamics of prestin that mediate eM. MD simulations showed that prestin samples a vast conformational landscape with expanded (ES) and compact (CS) states beyond previously reported prestin structures. Transition from CS to ES is dominated by the translational-rotational movement of prestin's transport domain, akin to elevator-type substrate translocation by related solute cNature communicationsElevator-like movements of prestin mediate outer hair cell electromotility.PMC10628124OL 240/8-1OL 240/4-219J20169MA 7525/2-1Haddad BGHartmann JLongo POliver DFuß AHuckschlag BMKuwabara MFLenz-Schwab DBerger TKMachtens JPQuestino AfalseElevator-like movements of prestin mediate outer hair cell electromotility.The outstanding acuity of the mammalian ear relies on cochlear amplification, an active mechanism based on the electromotility (eM) of outer hair cells. eM is a piezoelectric mechanism generated by little-understood, voltage-induced conformational changes of the anion transporter homolog prestin (SLC26A5). We used a combination of molecular dynamics (MD) simulations and biophysical approaches to identify the structural dynamics of prestin that mediate eM. MD simulations showed that prestin samples a vast conformational landscape with expanded (ES) and compact (CS) states beyond previously reported prestin structures. Transition from CS to ES is dominated by the translational-rotational movement of prestin's transport domain, akin to elevator-type substrate translocation by related solute c2023-01-01T00:00:00Z2023 Nov2026-05-28T22:28:52.506Z2025-02-19T00:01:20.441ZS-EPMC106281243793229410.1038/s41467-023-42489-8