한빛사논문
- 조회838
Hanbin Jeong # 1, Sarah Clark # 1, April Goehring 1 2, Sepehr Dehghani-Ghahnaviyeh 3 4 5, Ali Rasouli 3 4 5, Emad Tajkhorshid 3 4 5, Eric Gouaux 6 7
1Vollum Institute, Oregon Health and Science University, Portland, OR, USA.
2Howard Hughes Medical Institute, Oregon Health and Science University, Portland, OR, USA.
3Theoretical and Computational Biophysics Group, NIH Center for Macromolecular Modeling and Bioinformatics, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
4Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
5Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
6Vollum Institute, Oregon Health and Science University, Portland, OR, USA.
7Howard Hughes Medical Institute, Oregon Health and Science University, Portland, OR, USA.
#Contributed equally.
Corresponding author
Correspondence to Eric Gouaux.
Abstract
The initial step in the sensory transduction pathway underpinning hearing and balance in mammals involves the conversion of force into the gating of a mechanosensory transduction channel1. Despite the profound socioeconomic impacts of hearing disorders and the fundamental biological significance of understanding mechanosensory transduction, the composition, structure and mechanism of the mechanosensory transduction complex have remained poorly characterized. Here we report the single-particle cryo-electron microscopy structure of the native transmembrane channel-like protein 1 (TMC-1) mechanosensory transduction complex isolated from Caenorhabditis elegans. The two-fold symmetric complex is composed of two copies each of the pore-forming TMC-1 subunit, the calcium-binding protein CALM-1 and the transmembrane inner ear protein TMIE. CALM-1 makes extensive contacts with the cytoplasmic face of the TMC-1 subunits, whereas the single-pass TMIE subunits reside on the periphery of the complex, poised like the handles of an accordion. A subset of complexes additionally includes a single arrestin-like protein, arrestin domain protein (ARRD-6), bound to a CALM-1 subunit. Single-particle reconstructions and molecular dynamics simulations show how the mechanosensory transduction complex deforms the membrane bilayer and suggest crucial roles for lipid-protein interactions in the mechanism by which mechanical force is transduced to ion channel gating.
논문정보
- Research article
- 2022년 10월 (BRIC 등록일 2022-10-19)
- 국외 연구진
- 생명과학 > 구조생물 및 생물물리학
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