Structural dynamics in the evolution of a bilobed protein scaffold.
Structural dynamics in the evolution of a bilobed protein scaffold.
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双叶蛋白质支架进化的结构动力学。
DOI：
10.1073/pnas.2026165118
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发表时间：
2021-12-07
影响因子：
11.1
通讯作者：
Cordes T
中科院分区：
文献类型：
--
作者：
Gouridis G;Muthahari YA;de Boer M;Griffith DA;Tsirigotaki A;Tassis K;Zijlstra N;Xu R;Eleftheriadis N;Sugijo Y;Zacharias M;Dömling A;Karamanou S;Pozidis C;Economou A;Cordes T
蛋白质通过使用定制的结构动力学来进行许多复杂的生物功能。这些是如何从祖先肽中产生的分子细节仍然是个谜。大自然是如何利用相同的褶皱来实现功能多样化的呢？为了阐明这一点，我们分析了具有共同结构核心的双叶蛋白，该结构核心遍布生命之树，并参与多种生物功能，如转录，酶催化，膜转运和信号传导。在这里，我们表明，结构核心的结构动力学差异主要是通过终端添加在一个长期的演变。这使底物特异性多样化，并最终使生物功能多样化。新的生物物理工具允许蛋白质的结构动力学和这种动力学的约束合作伙伴的监管进行了前所未有的详细探讨。虽然这为蛋白质功能提供了重要的见解，但结构动力学指导蛋白质进化的方法仍然知之甚少。在这里，我们研究了如何与双叶结构的蛋白质，由两个相关的结构域的周质结合蛋白样II结构域家族，经历了不同的进化，导致其结构动力学的适应。我们对具有共同原始结构核心的600种双叶蛋白进行了结构分析，并辅以生物物理研究，通过单分子Förster共振能量转移和氢氘交换质谱法探索选定实例的结构动力学。我们表明，进化修饰的结构核心，主要是在其末端，使不同的结构动态，允许这些蛋白质的多样化成转录因子，酶，和胞质外转运相关蛋白。核心的结构修饰产生了结构域间的相互作用，稳定了结构状态，重塑了活性位点的几何形状，并最终改变了底物的特异性。我们的研究结果揭示了一个尚未认识到的机制，在长期的进化过程中出现的功能混杂，并适用于大量的域架构。
Proteins conduct numerous complex biological functions by use of tailored structural dynamics. The molecular details of how these emerged from ancestral peptides remains mysterious. How does nature utilize the same repertoire of folds to diversify function? To shed light on this, we analyzed bilobed proteins with a common structural core, which is spread throughout the tree of life and is involved in diverse biological functions such as transcription, enzymatic catalysis, membrane transport, and signaling. We show here that the structural dynamics of the structural core differentiate predominantly via terminal additions during a long-period evolution. This diversifies substrate specificity and, ultimately, biological function. Novel biophysical tools allow the structural dynamics of proteins and the regulation of such dynamics by binding partners to be explored in unprecedented detail. Although this has provided critical insights into protein function, the means by which structural dynamics direct protein evolution remain poorly understood. Here, we investigated how proteins with a bilobed structure, composed of two related domains from the periplasmic-binding protein–like II domain family, have undergone divergent evolution, leading to adaptation of their structural dynamics. We performed a structural analysis on ∼600 bilobed proteins with a common primordial structural core, which we complemented with biophysical studies to explore the structural dynamics of selected examples by single-molecule Förster resonance energy transfer and Hydrogen–Deuterium exchange mass spectrometry. We show that evolutionary modifications of the structural core, largely at its termini, enable distinct structural dynamics, allowing the diversification of these proteins into transcription factors, enzymes, and extracytoplasmic transport-related proteins. Structural embellishments of the core created interdomain interactions that stabilized structural states, reshaping the active site geometry, and ultimately altered substrate specificity. Our findings reveal an as-yet-unrecognized mechanism for the emergence of functional promiscuity during long periods of evolution and are applicable to a large number of domain architectures.
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影响因子：
5.6
作者：
Alicea I;Marvin JS;Miklos AE;Ellington AD;Looger LL;Schreiter ER
通讯作者：
Schreiter ER
DOI：
10.1073/pnas.82.15.5000
发表时间：
1985-01-01
影响因子：
11.1
作者：
ANSARI, A;BERENDZEN, J;YOUNG, RD
通讯作者：
YOUNG, RD
影响因子：
8.6
作者：
Clifton, Ben E.;Jackson, Colin J.
通讯作者：
Jackson, Colin J.
影响因子：
4.3
作者：
Bliven S;Lafita A;Parker A;Capitani G;Duarte JM
通讯作者：
Duarte JM
影响因子：
5.8
作者：
Arnold, K;Bordoli, L;Schwede, T
通讯作者：
Schwede, T