7V75

Thermostabilized human prestin in complex with salicylate

Summary for 7V75

• Entry DOI: 10.2210/pdb7v75/pdb
• EMDB information: 31759
• Descriptor: prestin, 2-HYDROXYBENZOIC ACID, CHOLESTEROL, ... (4 entities in total)
• Functional Keywords: motor protein, prestin, slc26a5, electromotility, membrane protein
• Biological source: Homo sapiens
• Total number of polymer chains: 1
• Total formula weight: 89495.41

Authors

Futamata, H.,Fukuda, M.,Yamashita, K.,Nishizawa, T.,Nureki, O. (deposition date: 2021-08-21, release date: 2022-08-31, Last modification date: 2024-06-12)

Primary citation

Futamata, H.,Fukuda, M.,Umeda, R.,Yamashita, K.,Tomita, A.,Takahashi, S.,Shikakura, T.,Hayashi, S.,Kusakizako, T.,Nishizawa, T.,Homma, K.,Nureki, O.
Cryo-EM structures of thermostabilized prestin provide mechanistic insights underlying outer hair cell electromotility.
Nat Commun, 13:6208-6208, 2022

PubMed Abstract: Outer hair cell elecromotility, driven by prestin, is essential for mammalian cochlear amplification. Here, we report the cryo-EM structures of thermostabilized prestin (Pres), 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 Pres 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.

PubMed: 36266333
DOI: 10.1038/s41467-022-34017-x

Experimental method

ELECTRON MICROSCOPY (3.57 Å)