8UC1

Cryo-EM structure of dolphin Prestin in low Cl buffer

8UC1 の概要

• エントリーDOI: 10.2210/pdb8uc1/pdb
• EMDBエントリー: 42112
• 分子名称: Prestin, CHLORIDE ION (2 entities in total)
• 機能のキーワード: solute carrier, electromotility, voltage sensitive, mechanosensitive, membrane protein
• 由来する生物種: Tursiops truncatus (common bottlenose dolphin)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 162018.41

構造登録者

Haller, P.,Bavi, N.,Perozo, E. (登録日: 2023-09-25, 公開日: 2023-12-13)

主引用文献

Lin, X.,Haller, P.R.,Bavi, N.,Faruk, N.,Perozo, E.,Sosnick, T.R.
Folding of prestin's anion-binding site and the mechanism of outer hair cell electromotility.
Elife, 12:-, 2023

PubMed Abstract: Prestin responds to transmembrane voltage fluctuations by changing its cross-sectional area, a process underlying the electromotility of outer hair cells and cochlear amplification. Prestin belongs to the SLC26 family of anion transporters yet is the only member capable of displaying electromotility. Prestin's voltage-dependent conformational changes are driven by the putative displacement of residue R399 and a set of sparse charged residues within the transmembrane domain, following the binding of a Cl anion at a conserved binding site formed by the amino termini of the TM3 and TM10 helices. However, a major conundrum arises as to how an anion that binds in proximity to a positive charge (R399), can promote the voltage sensitivity of prestin. Using hydrogen-deuterium exchange mass spectrometry, we find that prestin displays an unstable anion-binding site, where folding of the amino termini of TM3 and TM10 is coupled to Cl binding. This event shortens the TM3-TM10 electrostatic gap, thereby connecting the two helices, resulting in reduced cross-sectional area. These folding events upon anion binding are absent in SLC26A9, a non-electromotile transporter closely related to prestin. Dynamics of prestin embedded in a lipid bilayer closely match that in detergent micelle, except for a destabilized lipid-facing helix TM6 that is critical to prestin's mechanical expansion. We observe helix fraying at prestin's anion-binding site but cooperative unfolding of multiple lipid-facing helices, features that may promote prestin's fast electromechanical rearrangements. These results highlight a novel role of the folding equilibrium of the anion-binding site, and help define prestin's unique voltage-sensing mechanism and electromotility.

PubMed: 38054956
DOI: 10.7554/eLife.89635

実験手法

ELECTRON MICROSCOPY (3.4 Å)