Cryo-EM structures of thermostabilized prestin provide mechanistic insights underlying outer hair cell electromotility

Haon Futamata, Masahiro Fukuda, Rie Umeda, Keitaro Yamashita, Atsuhiro Tomita, Satoe Takahashi, Takafumi Shikakura, Shigehiko Hayashi, Tsukasa Kusakizako, Tomohiro Nishizawa*, Kazuaki Homma*, Osamu Nureki*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Outer hair cell elecromotility, driven by prestin, is essential for mammalian cochlear amplification. Here, we report the cryo-EM structures of thermostabilized prestin (PresTS), complexed with chloride, sulfate, or salicylate at 3.52-3.63 Å resolutions. The central positively-charged cavity allows flexible binding of various anion species, which likely accounts for the known distinct modulations of nonlinear capacitance (NLC) by different anions. Comparisons of these PresTS structures with recent prestin structures suggest rigid-body movement between the core and gate domains, and provide mechanistic insights into prestin inhibition by salicylate. Mutations at the dimeric interface severely diminished NLC, suggesting that stabilization of the gate domain facilitates core domain movement, thereby contributing to the expression of NLC. These findings advance our understanding of the molecular mechanism underlying mammalian cochlear amplification.

Original languageEnglish (US)
Article number6208
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • General
  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'Cryo-EM structures of thermostabilized prestin provide mechanistic insights underlying outer hair cell electromotility'. Together they form a unique fingerprint.

Cite this