Conformational Dynamics of Activation for the Pentameric Complex of Dimeric G Protein-Coupled Receptor and Heterotrimeric G Protein
Conformational Dynamics of Activation for the Pentameric Complex of Dimeric G Protein-Coupled Receptor and Heterotrimeric G Protein
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DOI：
10.1016/j.str.2012.03.017
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发表时间：
2012-05-09
期刊：
影响因子：
5.7
通讯作者：
Palczewski, Krzysztof
中科院分区：
文献类型：
--
作者：
Orban, Tivadar;Jastrzebska, Beata;Palczewski, Krzysztof
视紫红质（Rho）是一种G蛋白偶联受体，其光活化引起构象变化，为杆状G蛋白G（t）提供特异性结合位点。在这项工作中，我们采用结构质谱技术来阐明伴随着基态Rho的光活化的Rho（Rho（星星））和在五聚体之间的二聚体Rho（星星）和异三聚体G（t）的复合物的结构变化。Rho（星星）和（Rho（星星））（2）-G（t）复合物之间观察到的羟基自由基标记和氘吸收的差异表明，光活化导致Rho在G（t）偶联后的初始收紧之后的结构松弛。相比之下，复合物中的无核苷酸G（t）明显更容易被氘摄取，从而允许其接受GTP并介导复合物解离。因此，我们提供了直接的证据，在信号放大的关键步骤中，Rho（星星）和G（t）在（Rho（星星））（2）-G（t）复合物中偶联时表现出不同的构象变化。
Photoactivation of rhodopsin (Rho), a G protein-coupled receptor, causes conformational changes that provide a specific binding site for the rod G protein, G(t). In this work we employed structural mass spectrometry techniques to elucidate the structural changes accompanying transition of ground state Rho to photoactivated Rho (Rho(star)) and in the pentameric complex between dimeric Rho(star) and heterotrimeric G(t). Observed differences in hydroxyl radical labeling and deuterium uptake between Rho(star) and the (Rho(star))(2)-G(t) complex suggest that photoactivation causes structural relaxation of Rho following its initial tightening upon G(t) coupling. In contrast, nucleotide-free G(t) in the complex is significantly more accessible to deuterium uptake allowing it to accept GTP and mediating complex dissociation. Thus, we provide direct evidence that in the critical step of signal amplification, Rho(star) and G(t) exhibit dissimilar conformational changes when they are coupled in the (Rho(star))(2)-G(t) complex.