Surveying nonvisual arrestins reveals allosteric interactions between functional sites.
Surveying nonvisual arrestins reveals allosteric interactions between functional sites.
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抑制蛋白是在所有脊椎动物中表达的重要支架蛋白。它们在与活性 G 蛋白偶联受体 (GPCR) 结合后调节细胞信号转导事件，并触发活性 GPCR 的内吞作用。虽然抑制蛋白上的许多功能位点已被表征，但这些位点如何相互作用的问题尚未得到解答。我们使用各向异性网络模型（ANM）和协方差补充技术来调查非视觉视紫红质抑制蛋白的所有可用结构，以绘制结构变化和蛋白质结合如何影响其结构动力学。我们发现激活和网格蛋白结合对视紫红质抑制蛋白动力学有显着影响，并且这些动力学变化局限于少数遥远的功能位点。这些位点包括 α-螺旋 1、套索环、核定位结构域和 C 环侧的 C 结构域 β-折叠。我们的技术表明，网格蛋白结合和/或抑制蛋白的 GPCR 激活会扰乱这些位点的动态，而与结构变化无关。
Arrestins are important scaffolding proteins that are expressed in all vertebrate animals. They regulate cell signaling events upon binding to active G-protein coupled receptors (GPCR) and trigger endocytosis of active GPCRs. While many of the functional sites on arrestins have been characterized, the question of how these sites interact is unanswered. We used anisotropic network modelling (ANM) together with our covariance compliment techniques to survey all the available structures of the non-visual arrestins to map how structural changes and protein-binding affect their structural dynamics. We found that activation and clathrin binding have a marked effect on arrestin dynamics, and that these dynamics changes are localized to a small number of distant functional sites. These sites include α-helix 1, the lariat loop, nuclear localization domain, and the C-domain β-sheets on the C-loop side. Our techniques suggest that clathrin binding and/or GPCR activation of arrestin perturb the dynamics of these sites independent of structural changes.
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影响因子：
2.9
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