globalchange  > 气候变化与战略
DOI: 10.1073/pnas.1809251116
论文题名:
Diverse GPCRs exhibit conserved water networks for stabilization and activation
作者: Venkatakrishnan A.J.; Ma A.K.; Fonseca R.; Latorraca N.R.; Kelly B.; Betz R.M.; Asawa C.; Kobilka B.K.; Dror R.O.
刊名: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
出版年: 2019
卷: 116, 期:8
起始页码: 3288
结束页码: 3293
语种: 英语
英文关键词: Activation ; GPCR dynamics ; Molecular dynamics ; Polar network ; Simulation ; Water molecules
Scopus关键词: G protein coupled receptor ; ligand ; water ; G protein coupled receptor ; water ; Article ; comparative study ; crystal structure ; crystallography ; intracellular signaling ; ligand binding ; priority journal ; protein interaction ; simulation ; chemistry ; human ; protein conformation ; signal transduction ; stretching exercise ; structure activity relation ; X ray crystallography ; Crystallography, X-Ray ; Humans ; Ligands ; Muscle Stretching Exercises ; Protein Conformation ; Receptors, G-Protein-Coupled ; Signal Transduction ; Structure-Activity Relationship ; Water
英文摘要: G protein-coupled receptors (GPCRs) have evolved to recognize incredibly diverse extracellular ligands while sharing a common architecture and structurally conserved intracellular signaling partners. It remains unclear how binding of diverse ligands brings about GPCR activation, the common structural change that enables intracellular signaling. Here, we identify highly conserved networks of water-mediated interactions that play a central role in activation. Using atomic-level simulations of diverse GPCRs, we show that most of the water molecules in GPCR crystal structures are highly mobile. Several water molecules near the G protein-coupling interface, however, are stable. These water molecules form two kinds of polar networks that are conserved across diverse GPCRs: (i) a network that is maintained across the inactive and the active states and (ii) a network that rearranges upon activation. Comparative analysis of GPCR crystal structures independently confirms the striking conservation of water-mediated interaction networks. These conserved water-mediated interactions near the G protein-coupling region, along with diverse water-mediated interactions with extracellular ligands, have direct implications for structure-based drug design and GPCR engineering. © 2019 National Academy of Sciences. All Rights Reserved.
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资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/163566
Appears in Collections:气候变化与战略

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作者单位: Venkatakrishnan, A.J., Department of Computer Science, Stanford University, Stanford, CA 94305, United States, Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, United States, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, United States, Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, United States; Ma, A.K., Department of Computer Science, Stanford University, Stanford, CA 94305, United States, Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, United States, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, United States, Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, United States; Fonseca, R., Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, United States; Latorraca, N.R., Department of Computer Science, Stanford University, Stanford, CA 94305, United States, Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, United States, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, United States, Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, United States, Biophysics Program, Stanford University, Stanford, CA 94305, United States; Kelly, B., Department of Computer Science, Stanford University, Stanford, CA 94305, United States, Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, United States, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, United States, Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, United States; Betz, R.M., Department of Computer Science, Stanford University, Stanford, CA 94305, United States, Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, United States, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, United States, Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, United States, Biophysics Program, Stanford University, Stanford, CA 94305, United States; Asawa, C., Department of Computer Science, Stanford University, Stanford, CA 94305, United States, Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, United States, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, United States, Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, United States; Kobilka, B.K., Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, United States; Dror, R.O., Department of Computer Science, Stanford University, Stanford, CA 94305, United States, Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, United States, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, United States, Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, United States, Biophysics Program, Stanford University, Stanford, CA 94305, United States

Recommended Citation:
Venkatakrishnan A.J.,Ma A.K.,Fonseca R.,et al. Diverse GPCRs exhibit conserved water networks for stabilization and activation[J]. Proceedings of the National Academy of Sciences of the United States of America,2019-01-01,116(8)
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