Elevator-like movements of prestin mediate outer hair cell electromotility.

Autor: Kuwabara MF; Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps University Marburg, 35037, Marburg, Germany., Haddad BG; Institute of Biological Information Processing (IBI-1), Molekular- und Zellphysiologie, and JARA-HPC, Forschungszentrum Jülich, Jülich, Germany., Lenz-Schwab D; Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps University Marburg, 35037, Marburg, Germany., Hartmann J; Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps University Marburg, 35037, Marburg, Germany., Longo P; Institute of Biological Information Processing (IBI-1), Molekular- und Zellphysiologie, and JARA-HPC, Forschungszentrum Jülich, Jülich, Germany., Huckschlag BM; Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps University Marburg, 35037, Marburg, Germany., Fuß A; Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps University Marburg, 35037, Marburg, Germany., Questino A; Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps University Marburg, 35037, Marburg, Germany., Berger TK; Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps University Marburg, 35037, Marburg, Germany., Machtens JP; Institute of Biological Information Processing (IBI-1), Molekular- und Zellphysiologie, and JARA-HPC, Forschungszentrum Jülich, Jülich, Germany. j.machtens@fz-juelich.de.; Institute of Clinical Pharmacology, RWTH Aachen University, Aachen, Germany. j.machtens@fz-juelich.de., Oliver D; Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps University Marburg, 35037, Marburg, Germany. oliverd@staff.uni-marburg.de.; DFG Research Training Group, Membrane Plasticity in Tissue Development and Remodeling, GRK 2213, Philipps University, Marburg, Germany. oliverd@staff.uni-marburg.de.; Center for Mind, Brain and Behavior (CMBB), Universities of Marburg and Giessen, Marburg, Germany. oliverd@staff.uni-marburg.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Nov 06; Vol. 14 (1), pp. 7145. Date of Electronic Publication: 2023 Nov 06.
DOI: 10.1038/s41467-023-42489-8
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: