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-Structure paper
タイトル | Molecular mechanism of prestin electromotive signal amplification. |
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ジャーナル・号・ページ | Cell, Vol. 184, Issue 18, Page 4669-4679.e13, Year 2021 |
掲載日 | 2021年9月2日 |
著者 | Jingpeng Ge / Johannes Elferich / Sepehr Dehghani-Ghahnaviyeh / Zhiyu Zhao / Marc Meadows / Henrique von Gersdorff / Emad Tajkhorshid / Eric Gouaux / |
PubMed 要旨 | 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 ...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. |
リンク | Cell / PubMed:34390643 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.3 - 4.3 Å |
構造データ | EMDB-23329, PDB-7lgu: EMDB-23331, PDB-7lgw: EMDB-23334, PDB-7lh2: EMDB-23335, PDB-7lh3: |
化合物 | ChemComp-CL: ChemComp-CLR: ChemComp-OCT: ChemComp-D10: ChemComp-D12: ChemComp-HEX: ChemComp-HP6: ChemComp-C14: ChemComp-HOH: ChemComp-SAL: |
由来 |
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キーワード | MEMBRANE PROTEIN / transporter family / lipid interaction / high resolution |