Jingpeng Ge, Johannes Elferich, Sepehr Dehghani-Ghahnaviyeh, Zhiyu Zhao, Marc
Meadows, Henrique von Gersdorff, Emad Tajkhorshid, and Eric Gouaux.
Molecular mechanism of prestin electromotive signal amplification.
Cell, 184:4669-4679, 2021.
GE2021-ET
Hearing involves two fundamental processes: mechano-electrical
transduction and signal amplification. Despite decades of
studies, the molecular bases for both remain elusive. Here, we
show how prestin, the electromotive molecule of outer hair
cells (OHCs) that senses both voltage and membrane tension,
mediates signal amplification by coupling conformational
changes to alterations in membrane surface area. Cryoelectron
microscopy (cryo-EM) structures of human prestin bound with
chloride or salicylate at a common “anion site” adopt
contracted or expanded states, respectively. Prestin is
ensconced within a perimeter of well-ordered lipids, through
which it induces dramatic deformation in the membrane and
couples protein conformational changes to the bulk membrane.
Together with computational studies, we illustrate how the
anion site is allosterically coupled to changes in the
transmembrane domain cross-sectional area and the surrounding
membrane. These studies provide insight into OHC
electromotility by providing a structure-based mechanism of the
membrane motor prestin.
