The high-light-sensitivity mechanism and optogenetic properties of the bacteriorhodopsin-like channelrhodopsin GtCCR4

IF 14.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Cell Pub Date : 2024-09-03 DOI:10.1016/j.molcel.2024.08.016
Tatsuki Tanaka, Shoko Hososhima, Yo Yamashita, Teppei Sugimoto, Toshiki Nakamura, Shunta Shigemura, Wataru Iida, Fumiya K. Sano, Kazumasa Oda, Takayuki Uchihashi, Kota Katayama, Yuji Furutani, Satoshi P. Tsunoda, Wataru Shihoya, Hideki Kandori, Osamu Nureki
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Abstract

Channelrhodopsins are microbial light-gated ion channels that can control the firing of neurons in response to light. Among several cation channelrhodopsins identified in Guillardia theta (GtCCRs), GtCCR4 has higher light sensitivity than typical channelrhodopsins. Furthermore, GtCCR4 shows superior properties as an optogenetic tool, such as minimal desensitization. Our structural analyses of GtCCR2 and GtCCR4 revealed that GtCCR4 has an outwardly bent transmembrane helix, resembling the conformation of activated G-protein-coupled receptors. Spectroscopic and electrophysiological comparisons suggested that this helix bend in GtCCR4 omits channel recovery time and contributes to high light sensitivity. An electrophysiological comparison of GtCCR4 and the well-characterized optogenetic tool ChRmine demonstrated that GtCCR4 has superior current continuity and action-potential spike generation with less invasiveness in neurons. We also identified highly active mutants of GtCCR4. These results shed light on the diverse structures and dynamics of microbial rhodopsins and demonstrate the strong optogenetic potential of GtCCR4.

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类细菌视紫红质通道视紫红质 GtCCR4 的高光敏机制和光遗传特性
通道闪烁蛋白是微生物的光门控离子通道,可以控制神经元对光的反应而发射。在Guillardia theta(GtCCRs)中发现的几种阳离子通道闪烁蛋白中,GtCCR4比典型的通道闪烁蛋白具有更高的光敏感性。此外,作为光遗传工具,GtCCR4 还显示出卓越的特性,如最小脱敏。我们对 GtCCR2 和 GtCCR4 的结构分析表明,GtCCR4 有一个向外弯曲的跨膜螺旋,类似于激活的 G 蛋白偶联受体的构象。光谱学和电生理学比较表明,GtCCR4 的这种螺旋弯曲省略了通道恢复时间,有助于提高光敏感性。对 GtCCR4 和特性良好的光遗传工具 ChRmine 的电生理学比较表明,GtCCR4 具有更优越的电流连续性和动作电位尖峰产生能力,对神经元的侵袭性更小。我们还发现了 GtCCR4 的高活性突变体。这些结果揭示了微生物视紫红质的不同结构和动力学,并证明了 GtCCR4 强大的光遗传潜力。
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来源期刊
Molecular Cell
Molecular Cell 生物-生化与分子生物学
CiteScore
26.00
自引率
3.80%
发文量
389
审稿时长
1 months
期刊介绍: Molecular Cell is a companion to Cell, the leading journal of biology and the highest-impact journal in the world. Launched in December 1997 and published monthly. Molecular Cell is dedicated to publishing cutting-edge research in molecular biology, focusing on fundamental cellular processes. The journal encompasses a wide range of topics, including DNA replication, recombination, and repair; Chromatin biology and genome organization; Transcription; RNA processing and decay; Non-coding RNA function; Translation; Protein folding, modification, and quality control; Signal transduction pathways; Cell cycle and checkpoints; Cell death; Autophagy; Metabolism.
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