Author: ["Peng Jin","David Bulkley","Yanmeng Guo","Wei Zhang","Zhenhao Guo","Walter Huynh","Shenping Wu","Shan Meltzer","Tong Cheng","Lily Yeh Jan","Yuh-Nung Jan","Yifan Cheng"]
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Abstract
Single-particle electron cryo-microscopy analysis of the mechanotransduction channel NOMPC reveals that it contains a bundle of four helical spring-shaped ankyrin repeat domains that undergo motion, potentially allowing mechanical movement of the cytoskeleton to be coupled to the opening of the channel. Mechanosensation forms the basis of many of our senses, including touch, balance, hearing and pain. Mechanically gated ion channels are responsible for transmitting mechanical force into electrical signals. However, how this occurs is not well understood at the molecular level. Here the authors report the structure of the Drosophila mechanotransduction channel NOMPC by single-particle cryo-electron microscopy. The channel contains a long, helical domain of ankyrin repeats, which appears to undergo a spring-like motion. This motion allows the mechanical movement of the cytoskeleton to be relayed into opening the channel. Mechanosensory transduction for senses such as proprioception, touch, balance, acceleration, hearing and pain relies on mechanotransduction channels, which convert mechanical stimuli into electrical signals in specialized sensory cells1. How force gates mechanotransduction channels is a central question in the field, for which there are two major models. One is the membrane-tension model: force applied to the membrane generates a change in membrane tension that is sufficient to gate the channel, as in the bacterial MscL channel and certain eukaryotic potassium channels2,3,4,5. The other is the tether model: force is transmitted via a tether to gate the channel. The transient receptor potential (TRP) channel NOMPC is important for mechanosensation-related behaviours such as locomotion, touch and sound sensation across different species including Caenorhabditis elegans6, Drosophila7,8,9 and zebrafish10. NOMPC is the founding member of the TRPN subfamily11, and is thought to be gated by tethering of its ankyrin repeat domain to microtubules of the cytoskeleton12,13,14,15. Thus, a goal of studying NOMPC is to reveal the underlying mechanism of force-induced gating, which could serve as a paradigm of the tether model. NOMPC fulfils all the criteria that apply to mechanotransduction channels1,7 and has 29 ankyrin repeats, the largest number among TRP channels. A key question is how the long ankyrin repeat domain is organized as a tether that can trigger channel gating. Here we present a de novo atomic structure of Drosophila NOMPC determined by single-particle electron cryo-microscopy. Structural analysis suggests that the ankyrin repeat domain of NOMPC resembles a helical spring, suggesting its role of linking mechanical displacement of the cytoskeleton to the opening of the channel. The NOMPC architecture underscores the basis of translating mechanical force into an electrical signal within a cell.Cite this article
Jin, P., Bulkley, D., Guo, Y. et al. Electron cryo-microscopy structure of the mechanotransduction channel NOMPC. Nature 547, 118–122 (2017). https://doi.org/10.1038/nature22981 