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Elevator-like movements of prestin mediate outer hair cell electromotility
by
Huckschlag, Britt-Marie
, Machtens, Jan-Philipp
, Berger, Thomas K.
, Haddad, Bassam G.
, Longo, Piersilvio
, Hartmann, Julia
, Fuß, Anneke
, Kuwabara, Makoto F.
, Questino, Annalisa
, Lenz-Schwab, Dominik
, Oliver, Dominik
in
14
/ 14/34
/ 631/443/376
/ 631/535/1267
/ 631/57/2270/1140
/ 631/57/2283
/ 9/74
/ Acuity
/ Cochlea
/ Crosslinking
/ Cysteine
/ Electric potential
/ Fluorimetry
/ Fluorometry
/ Hair
/ Hair cells
/ Humanities and Social Sciences
/ Ion transport
/ Membranes
/ Molecular dynamics
/ multidisciplinary
/ Outer hair cells
/ Piezoelectricity
/ Science
/ Science (multidisciplinary)
/ Simulation
/ Substrates
/ Translocation
/ Voltage
2023
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Elevator-like movements of prestin mediate outer hair cell electromotility
by
Huckschlag, Britt-Marie
, Machtens, Jan-Philipp
, Berger, Thomas K.
, Haddad, Bassam G.
, Longo, Piersilvio
, Hartmann, Julia
, Fuß, Anneke
, Kuwabara, Makoto F.
, Questino, Annalisa
, Lenz-Schwab, Dominik
, Oliver, Dominik
in
14
/ 14/34
/ 631/443/376
/ 631/535/1267
/ 631/57/2270/1140
/ 631/57/2283
/ 9/74
/ Acuity
/ Cochlea
/ Crosslinking
/ Cysteine
/ Electric potential
/ Fluorimetry
/ Fluorometry
/ Hair
/ Hair cells
/ Humanities and Social Sciences
/ Ion transport
/ Membranes
/ Molecular dynamics
/ multidisciplinary
/ Outer hair cells
/ Piezoelectricity
/ Science
/ Science (multidisciplinary)
/ Simulation
/ Substrates
/ Translocation
/ Voltage
2023
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Elevator-like movements of prestin mediate outer hair cell electromotility
by
Huckschlag, Britt-Marie
, Machtens, Jan-Philipp
, Berger, Thomas K.
, Haddad, Bassam G.
, Longo, Piersilvio
, Hartmann, Julia
, Fuß, Anneke
, Kuwabara, Makoto F.
, Questino, Annalisa
, Lenz-Schwab, Dominik
, Oliver, Dominik
in
14
/ 14/34
/ 631/443/376
/ 631/535/1267
/ 631/57/2270/1140
/ 631/57/2283
/ 9/74
/ Acuity
/ Cochlea
/ Crosslinking
/ Cysteine
/ Electric potential
/ Fluorimetry
/ Fluorometry
/ Hair
/ Hair cells
/ Humanities and Social Sciences
/ Ion transport
/ Membranes
/ Molecular dynamics
/ multidisciplinary
/ Outer hair cells
/ Piezoelectricity
/ Science
/ Science (multidisciplinary)
/ Simulation
/ Substrates
/ Translocation
/ Voltage
2023
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Elevator-like movements of prestin mediate outer hair cell electromotility
Journal Article
Elevator-like movements of prestin mediate outer hair cell electromotility
2023
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Overview
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.
Probing the molecular dynamics of the membrane motor, prestin, with biophysical measures and MD simulations, Kuwabara et al. find that an elevator-like domain movement across the membrane produces the unique piezoelectric behavior.
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