溶液核磁共振波谱技术在两畴钙结合蛋白动力学研究中的应用

IF 2.624
Roberto Kopke Salinas
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引用次数: 1

摘要

由于柔性连接体连接刚性结构域的蛋白质动力学可能对多种生物系统的功能至关重要,包括从膜转运体到钙信号传导和细胞间连接的形成。考虑到核磁共振波谱在各种时间尺度上的动力学特征是非常强大的,本文概述了用于表征相关生物系统中域间动力学的主要策略。重点是钙结合蛋白:钙调蛋白、钙粘蛋白和Na+/Ca2+交换器钙传感器结构域。在抗磁性蛋白质中引入顺磁中心被认为是获得关于结构域间动力学的明确信息的关键。这是因为在多结构域蛋白质中,其中一个结构域的自对准避免了处理动态系统中对准张量波动的问题。残差偶极耦合(rdc)和伪接触位移(PCSs)与计算策略的结合,旨在提供蛋白质动力学的整体描述,被认为是获得详细的域间运动原子信息的最有效策略。值得注意的是,钙粘蛋白外结构域和Na+/Ca2+交换器钙传感器在钙结合时以相同的方式响应:在没有钙的情况下,两个结构域彼此灵活地连接在一起,并可能优先样品弯曲的结构域间排列,而钙结合稳定了刚性和扩展的结构域间排列。因此,值得注意的是,大自然选择了相同的分子机制来促进钙信号触发的两种截然不同的生物功能:钙粘蛋白二聚体形成的细胞间粘附和Na+/Ca2+交换器中膜转运体的变构调节。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The application of solution NMR spectroscopy to study dynamics of two-domain calcium-binding proteins

The application of solution NMR spectroscopy to study dynamics of two-domain calcium-binding proteins

Protein dynamics due to flexible linkers connecting otherwise rigid domains may be critical for the functioning of a variety of biological systems, ranging from membrane transporters to calcium-signaling and the formation of intercellular junctions. Considering that NMR spectroscopy is extremely powerful to characterize dynamics at various time scales, this manuscript brings an overview of the main strategies that have been employed to characterize inter-domain dynamics in relevant biological systems. Emphasis was given to the calcium binding proteins: calmodulin, cadherin, and the Na+/Ca2+ exchanger calcium-sensor domain. The introduction of paramagnetic centers in diamagnetic proteins is seen as key to obtaining unambiguous information about inter-domain dynamics. This is because the self-alignment of one of the domains in multi-domain proteins avoids the problem of dealing with alignment tensor fluctuations in dynamic systems. The combination of residual dipolar couplings (RDCs) and pseudocontact shifts (PCSs) with computational strategies aiming to provide an ensemble description of protein dynamics is seen as the most powerful strategy to gain detailed atomistic information on inter-domain motions. It is noteworthy that the cadherin ectodomains and the Na+/Ca2+ exchanger calcium sensor respond in the same way upon calcium-binding: in the absence of calcium the two domains are flexibly linked to one another and may preferentially sample kinked inter-domain arrangements, while calcium binding stabilizes a rigid and extended inter-domain arrangement. It is thus remarkable that nature chose the same molecular mechanism to promote two very different biological functions that are triggered by calcium signaling: intercellular adhesion by the formation of cadherin dimers and the allosteric regulation of a membrane transporter in the case of the Na+/Ca2+ exchanger.

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