G 蛋白偶联受体的结构生物学：XFEL 和 cryoEM 带来的新机遇。
Structural biology of G protein-coupled receptors: new opportunities from XFELs and cryoEM.
机构信息
Department of Chemistry, Bridge Institute, University of Southern California, Los Angeles, CA 90089, USA.
SLAC National Accelerator Laboratory, Bioscience Division, Menlo Park, CA 94025, USA; Stanford University, Department of Structural Biology, Stanford, CA 94305, USA.
出版信息
Curr Opin Struct Biol. 2018 Aug;51:44-52. doi: 10.1016/j.sbi.2018.03.009. Epub 2018 Mar 16.
Abstract
G protein-coupled receptors mediate cell signaling and regulate the majority of sensory and physiological processes in the human body. Recent breakthroughs in cryo-electron microscopy and X-ray free electron lasers have accelerated structural studies of difficult-to-crystallize receptors and their signaling complexes, and have opened up new opportunities in understanding conformational dynamics and visualizing the process of receptor activation with unprecedented spatial and temporal resolution. Here, we summarize major milestones and challenges associated with the application of these techniques and outline future directions in their development with a focus on membrane protein structural biology.
摘要
G 蛋白偶联受体介导细胞信号转导，调节人体大部分感觉和生理过程。近年来，冷冻电子显微镜和自由电子 X 射线激光技术的突破加速了难结晶受体及其信号复合物的结构研究，为理解构象动力学和以前所未有的时空分辨率可视化受体激活过程提供了新的机会。在这里，我们总结了这些技术应用的主要里程碑和挑战，并概述了其发展的未来方向，重点是膜蛋白结构生物学。
相似文献
1
Structural biology of G protein-coupled receptors: new opportunities from XFELs and cryoEM.G 蛋白偶联受体的结构生物学：XFEL 和 cryoEM 带来的新机遇。
Curr Opin Struct Biol. 2018 Aug;51:44-52. doi: 10.1016/j.sbi.2018.03.009. Epub 2018 Mar 16.
2
Recent advances in the determination of G protein-coupled receptor structures.近年来 G 蛋白偶联受体结构测定的进展。
Curr Opin Struct Biol. 2018 Aug;51:28-34. doi: 10.1016/j.sbi.2018.03.002. Epub 2018 Mar 13.
3
Serial Femtosecond Crystallography of G Protein-Coupled Receptors.G 蛋白偶联受体的连续飞秒晶体学。
Annu Rev Biophys. 2018 May 20;47:377-397. doi: 10.1146/annurev-biophys-070317-033239. Epub 2018 Mar 15.
4
Structural biology: 'seeing' crystals the XFEL way.结构生物学：用 XFEL 看到晶体。
Nat Methods. 2014 Sep;11(9):903-8. doi: 10.1038/nmeth.3070.
5
Structure determination of GPCRs: cryo-EM compared with X-ray crystallography.G 蛋白偶联受体（GPCRs）结构的确定：冷冻电镜与 X 射线晶体学的比较。
Biochem Soc Trans. 2021 Nov 1;49(5):2345-2355. doi: 10.1042/BST20210431.
6
NMR analysis of GPCR conformational landscapes and dynamics.NMR 分析 GPCR 构象景观和动态。
Mol Cell Endocrinol. 2019 Mar 15;484:69-77. doi: 10.1016/j.mce.2018.12.019. Epub 2019 Jan 25.
7
New approaches towards the understanding of integral membrane proteins: A structural perspective on G protein-coupled receptors.理解整合膜蛋白的新方法：G蛋白偶联受体的结构视角
Protein Sci. 2017 Aug;26(8):1493-1504. doi: 10.1002/pro.3200. Epub 2017 Jun 7.
8
Cryo-EM advances in GPCR structure determination.冷冻电镜技术在 G 蛋白偶联受体结构测定方面的进展。
J Biochem. 2024 Jul 1;176(1):1-10. doi: 10.1093/jb/mvae029.
9
Peptide recognition, signaling and modulation of class B G protein-coupled receptors.B 类 G 蛋白偶联受体的肽识别、信号转导和调节。
Curr Opin Struct Biol. 2018 Aug;51:53-60. doi: 10.1016/j.sbi.2018.03.008. Epub 2018 Mar 19.
10
Structural biology: The gatekeepers revealed.结构生物学：揭秘守门人。
Nature. 2010 Jun 10;465(7299):823-6. doi: 10.1038/465823a.
引用本文的文献
1
Ligand-Induced Biased Activation of GPCRs: Recent Advances and New Directions from In Silico Approaches.G蛋白偶联受体的配体诱导偏向性激活：计算机模拟方法的最新进展与新方向
Molecules. 2025 Feb 25;30(5):1047. doi: 10.3390/molecules30051047.
2
Thermodynamic role of receptor phosphorylation barcode in cannabinoid receptor desensitization.受体磷酸化条形码在大麻素受体脱敏中的热力学作用。
Biochem Biophys Res Commun. 2025 Jan;743:151100. doi: 10.1016/j.bbrc.2024.151100. Epub 2024 Nov 29.
3
Differential Behavior of Conformational Dynamics in Active and Inactive States of Cannabinoid Receptor 1.大麻素受体 1 活性状态和非活性状态构象动力学的差异行为。
J Phys Chem B. 2024 Sep 5;128(35):8437-8447. doi: 10.1021/acs.jpcb.4c02828. Epub 2024 Aug 22.
4
G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.G 蛋白偶联受体（GPCRs）：结构、机制和药物发现方面的进展。
Signal Transduct Target Ther. 2024 Apr 10;9(1):88. doi: 10.1038/s41392-024-01803-6.
5
A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers.一种用于在 X 射线自由电子激光上进行时间分辨连续蛋白质晶体学和化合物筛选的多储库挤出机。
Nat Commun. 2023 Dec 2;14(1):7956. doi: 10.1038/s41467-023-43523-5.
6
Evolution of Sequence and Structure of SARS-CoV-2 Spike Protein: A Dynamic Perspective.严重急性呼吸综合征冠状病毒2刺突蛋白的序列与结构演变：动态视角
ACS Omega. 2023 Jun 21;8(26):23283-23304. doi: 10.1021/acsomega.3c00944. eCollection 2023 Jul 4.
7
Characterization of synthetic antigen binding fragments targeting Toc75 for the isolation of TOC in A. thaliana and P. sativum.鉴定针对Toc75 的合成抗原结合片段，用于从拟南芥和向日葵中分离 TOC。
Structure. 2023 May 4;31(5):595-606.e5. doi: 10.1016/j.str.2023.03.002. Epub 2023 Mar 27.
8
Serial femtosecond crystallography.串行飞秒晶体学
Nat Rev Methods Primers. 2022 Aug 4;2. doi: 10.1038/s43586-022-00141-7.
9
Electrically stimulated droplet injector for reduced sample consumption in serial crystallography.用于串行晶体学中减少样品消耗的电刺激液滴注射器。
Biophys Rep (N Y). 2022 Sep 29;2(4):100081. doi: 10.1016/j.bpr.2022.100081. eCollection 2022 Dec 14.
10
MicroED structure of the human adenosine receptor determined from a single nanocrystal in LCP.从 LCP 中的单个纳米晶体测定的人腺苷受体的 MicroED 结构。
Proc Natl Acad Sci U S A. 2021 Sep 7;118(36). doi: 10.1073/pnas.2106041118.
本文引用的文献
1
Cryo-EM structure of the adenosine A receptor coupled to an engineered heterotrimeric G protein.冷冻电镜结构解析腺苷 A 受体与工程化异源三聚体 G 蛋白偶联。
Elife. 2018 May 4;7:e35946. doi: 10.7554/eLife.35946.
2
Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex.偏向激动剂结合的人 GLP-1 受体-Gs 复合物的相衬 cryo-EM 结构。
Nature. 2018 Mar 1;555(7694):121-125. doi: 10.1038/nature25773. Epub 2018 Feb 21.
3
Viscous hydrophilic injection matrices for serial crystallography.用于串行晶体学的粘性亲水性注射基质。
IUCrJ. 2017 May 5;4(Pt 4):400-410. doi: 10.1107/S2052252517005140. eCollection 2017 Jul 1.
4
XFELs for structure and dynamics in biology.用于生物学结构与动力学研究的X射线自由电子激光
IUCrJ. 2017 May 10;4(Pt 4):322-339. doi: 10.1107/S2052252517005760. eCollection 2017 Jul 1.
5
Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors.鉴定G蛋白偶联受体招募抑制蛋白的磷酸化编码
Cell. 2017 Jul 27;170(3):457-469.e13. doi: 10.1016/j.cell.2017.07.002.
6
Structural insights into the extracellular recognition of the human serotonin 2B receptor by an antibody.结构洞察人类血清素 2B 受体的细胞外识别抗体。
Proc Natl Acad Sci U S A. 2017 Aug 1;114(31):8223-8228. doi: 10.1073/pnas.1700891114. Epub 2017 Jul 17.
7
Cryo-EM structure of haemoglobin at 3.2 Å determined with the Volta phase plate.采用 Volta 相板技术获得的 3.2 Å 分辨率血影蛋白冷冻电镜结构。
Nat Commun. 2017 Jun 30;8:16099. doi: 10.1038/ncomms16099.
8
Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein.与G蛋白复合物结合的活化胰高血糖素样肽-1受体的冷冻电镜结构
Nature. 2017 Jun 8;546(7657):248-253. doi: 10.1038/nature22394. Epub 2017 May 24.
9
Structure of the full-length glucagon class B G-protein-coupled receptor.全长胰高血糖素B类G蛋白偶联受体的结构
Nature. 2017 Jun 8;546(7657):259-264. doi: 10.1038/nature22363. Epub 2017 May 17.
10
Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand.多结构域人 smoothened 受体与超级稳定配体复合物的晶体结构。
Nat Commun. 2017 May 17;8:15383. doi: 10.1038/ncomms15383.
Zotero 插件