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光敏膜蛋白作为精准治疗工具的研究进展

Light-Sensitive Membrane Proteins as Tools to Generate Precision Treatments.

机构信息

Department of Biology, ETH Zürich, 8093, Zurich, Switzerland.

Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, 5232, Villigen, Switzerland.

出版信息

J Membr Biol. 2020 Apr;253(2):81-86. doi: 10.1007/s00232-020-00115-4. Epub 2020 Apr 4.

DOI:10.1007/s00232-020-00115-4
PMID:32248246
Abstract

INTRODUCTION BY ANA-NICOLETA BONDAR, BIOPHYSICS SECTION HEAD EDITOR: This issue of the Journal of Membrane Biology inaugurates Up-and-Coming Scientist, in which investigators at early career stages are invited to present recent research in the broad context of their discipline. We inaugurate Up-and-Coming Scientist with the essay by Dr. Elena Lesca of the ETH Zürich and the Paul Scherrer Institut, Switzerland. Dr. Lesca has completed her doctoral degree at the Technical University München, Germany, in 2014, and pursued postdoctoral research at the ETH Zürich and Paul Scherrer Institut, where she is Senior Assistant since 2019. Two recent papers by Dr. Lesca et al. (references 33 and 39) have used X-ray crystallography and experimental biophysics approaches to shed light on the mechanism of action of a membrane receptor from the G Protein-Coupled Receptor (GPCR) family, Jumping Spider Rhodopsin-1 (JSR-1). JSR-1 is a visual rhodopsin activated upon absorption of light by its covalently bound retinal chromophore. Unlike the better-understood bovine rhodopsin GPCR, which is monostable, JSR-1 is bistable (i.e., in JSR-1 the Schiff base that binds retinal to the protein stays protonated throughout the reaction cycle), and absorption of a second photon resets the retinal ligand to the resting state configuration. In her essay, Dr. Lesca discusses the implications of her work on JSR-1 and, more broadly, GPCR research, for state-of-the-art applications in optogenetics and drug design.

摘要

简介

生物物理分部主编安娜-妮可塔·邦达尔博士:本期《膜生物学杂志》推出了崭露头角的科学家,邀请处于职业生涯早期的研究人员在其学科的广泛背景下介绍最近的研究。我们邀请瑞士苏黎世联邦理工学院和保罗谢勒研究所的埃琳娜·莱斯卡博士在崭露头角的科学家栏目中发表文章。莱斯卡博士于 2014 年在德国慕尼黑工业大学完成博士学位,随后在苏黎世联邦理工学院和保罗谢勒研究所从事博士后研究,自 2019 年以来一直担任高级助理。莱斯卡博士等人最近发表的两篇论文(参考文献 33 和 39)使用 X 射线晶体学和实验生物物理学方法揭示了 G 蛋白偶联受体(GPCR)家族膜受体的作用机制,即跳跃蜘蛛视紫红质-1(JSR-1)。JSR-1 是一种视觉视紫红质,在其共价结合的视黄醛发色团吸收光后被激活。与更好理解的单稳定牛视紫红质 GPCR 不同,JSR-1 是双稳定的(即,在 JSR-1 中,结合视蛋白的席夫碱在整个反应循环中保持质子化),吸收第二个光子将视黄醛配体重置为静止状态构型。在她的文章中,莱斯卡博士讨论了她在 JSR-1 以及更广泛的 GPCR 研究方面的工作对光遗传学和药物设计的最先进应用的意义。

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本文引用的文献

1
Rules of Engagement: GPCRs and G Proteins.作用机制:G蛋白偶联受体与G蛋白
ACS Pharmacol Transl Sci. 2018 Sep 7;1(2):73-83. doi: 10.1021/acsptsci.8b00026. eCollection 2018 Nov 9.
2
Crystal structure of jumping spider rhodopsin-1 as a light sensitive GPCR.跳蛛视紫红质-1 的晶体结构作为一种光敏感 G 蛋白偶联受体。
Proc Natl Acad Sci U S A. 2019 Jul 16;116(29):14547-14556. doi: 10.1073/pnas.1902192116. Epub 2019 Jun 27.
3
Utilization of Biased G Protein-Coupled ReceptorSignaling towards Development of Safer andPersonalized Therapeutics.
利用偏向的 G 蛋白偶联受体信号转导开发更安全和个体化的治疗药物。
Molecules. 2019 May 29;24(11):2052. doi: 10.3390/molecules24112052.
4
The counterion-retinylidene Schiff base interaction of an invertebrate rhodopsin rearranges upon light activation.无脊椎动物视紫红质的抗衡离子-视黄醛亚胺席夫碱相互作用在光激活时会发生重排。
Commun Biol. 2019 May 13;2:180. doi: 10.1038/s42003-019-0409-3. eCollection 2019.
5
Structures of the M1 and M2 muscarinic acetylcholine receptor/G-protein complexes.M1 和 M2 毒蕈碱型乙酰胆碱受体/G 蛋白复合物的结构。
Science. 2019 May 10;364(6440):552-557. doi: 10.1126/science.aaw5188.
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Biased Signaling of the Mu Opioid Receptor Revealed in Native Neurons.天然神经元中μ阿片受体的偏向性信号传导
iScience. 2019 Apr 26;14:47-57. doi: 10.1016/j.isci.2019.03.011. Epub 2019 Mar 15.
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The Two-Photon Reversible Reaction of the Bistable Jumping Spider Rhodopsin-1.双光子可逆反应的二稳态跳跃蜘蛛视紫红质-1。
Biophys J. 2019 Apr 2;116(7):1248-1258. doi: 10.1016/j.bpj.2019.02.025. Epub 2019 Mar 5.
8
Distinct G protein-coupled receptor phosphorylation motifs modulate arrestin affinity and activation and global conformation.不同的 G 蛋白偶联受体磷酸化基序调节阻滞蛋白的亲和力和激活以及整体构象。
Nat Commun. 2019 Mar 19;10(1):1261. doi: 10.1038/s41467-019-09204-y.
9
GPCR Signaling Regulation: The Role of GRKs and Arrestins.G蛋白偶联受体信号转导调控:G蛋白偶联受体激酶和抑制蛋白的作用
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Binding kinetics of ligands acting at GPCRs.作用于 G 蛋白偶联受体的配体的结合动力学。
Mol Cell Endocrinol. 2019 Apr 5;485:9-19. doi: 10.1016/j.mce.2019.01.018. Epub 2019 Feb 8.