Elevator-like movements of prestin mediate outer hair cell electromotility

Makoto F. Kuwabara, Bassam G. Haddad, Dominik Lenz-Schwab, Julia Hartmann, Piersilvio Longo, Britt-Marie Huckschlag, Anneke Fuß, Annalisa Questino, Thomas K. Berger, Jan-Philipp Machtens () and Dominik Oliver ()
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Makoto F. Kuwabara: Philipps University Marburg
Bassam G. Haddad: Forschungszentrum Jülich
Dominik Lenz-Schwab: Philipps University Marburg
Julia Hartmann: Philipps University Marburg
Piersilvio Longo: Forschungszentrum Jülich
Britt-Marie Huckschlag: Philipps University Marburg
Anneke Fuß: Philipps University Marburg
Annalisa Questino: Philipps University Marburg
Thomas K. Berger: Philipps University Marburg
Jan-Philipp Machtens: Forschungszentrum Jülich
Dominik Oliver: Philipps University Marburg

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract 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 carriers. Reversible transition between CS and ES states was supported experimentally by cysteine accessibility scanning, cysteine cross-linking between transport and scaffold domains, and voltage-clamp fluorometry (VCF). Our data demonstrate that prestin’s piezoelectric dynamics recapitulate essential steps of a structurally conserved ion transport cycle.

Date: 2023
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DOI: 10.1038/s41467-023-42489-8

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