<br>生物信息分析和生物物理表征揭示 G0S2 蛋白的结构紊乱,ACS Omega

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生物信息分析和生物物理表征揭示 G0S2 蛋白的结构紊乱
ACS Omega ( IF 3.7 ) Pub Date : 2020-10-05 , DOI: 10.1021/acsomega.0c03171
Edgar D Páez-Pérez ₁ , Miriam Livier Llamas-García ₁ , Claudia G Benítez-Cardoza ₂ , Gabriela M Montero-Morán ₃ , Samuel Lara-González ₁

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G0S2 是一种长度为 103 个残基的小蛋白质，参与多种细胞过程。迄今为止，一些报告表明 G0S2 通过与关键蛋白质进行直接的蛋白质-蛋白质相互作用来发挥作用。在脂肪分解过程中，G0S2 与脂肪甘油三酯脂肪酶特异性相互作用，抑制其活性，导致脂肪分解下调。类似地，G0S2也参与细胞凋亡、细胞增殖和氧化磷酸化的调节；然而，有关 G0S2 结构和生物物理特性的信息有限。在这项工作中，我们对人类和小鼠 G0S2 蛋白进行了比较结构分析。生物信息学表明人 G0S2 中存在无序的 C 末端区域。通过尺寸排阻色谱和动态光散射进行的实验表征表明，人和小鼠 G0S2 具有不同的流体动力学特性。与行为类似于球状蛋白的小鼠 G0S2 相比，人类 G0S2 显示出拉长的构象，很可能是通过显示无序的 C 末端区域来实现的。对变性条件下的流体动力学特性的进一步分析表明，小鼠蛋白质中存在一种结构元件，该结构元件在低尿素浓度下经历有序到无序的转变。圆二色性结构分析表明，在天然条件下，两种蛋白质主要是非结构化的，显示出β片层结构的存在。 CD 数据的进一步分析表明，这两种蛋白质都属于本质上无序蛋白质的前熔球家族。我们认为，在 G0S2 蛋白中观察到的内在紊乱可能促进其在细胞代谢调节中与多个伙伴的相互作用。

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Bioinformatic Analysis and Biophysical Characterization Reveal Structural Disorder in G0S2 Protein

G0S2 is a small protein of 103 residues in length that is involved in multiple cellular processes. To date, several reports have shown that G0S2 functions by making direct protein–protein interactions with key proteins. In lipolysis, G0S2 specifically interacts with adipose triglyceride lipase, inhibiting its activity and resulting in lipolysis being downregulated. In a similar way, G0S2 also participates in the regulation of apoptosis, cell proliferation, and oxidative phosphorylation; however, information regarding G0S2 structural and biophysical properties is limited. In this work, we conducted a comparative structural analysis of human and mouse G0S2 proteins. Bioinformatics suggests the presence of a disordered C-terminal region in human G0S2. Experimental characterization by size-exclusion chromatography and dynamic light scattering showed that human and mouse G0S2 have different hydrodynamic properties. In comparison to the mouse G0S2, which behaves similar to a globular protein, the human G0S2 shows an elongated conformation, most likely by displaying a disordered C-terminal region. Further analysis of hydrodynamic properties under denaturing conditions suggests the presence of a structural element in the mouse protein that undergoes an order to disorder transition at low urea concentration. Structural analysis by circular dichroism revealed that in native conditions, both proteins are mainly unstructured, showing the presence of beta sheet structures. Further analysis of CD data suggests that both proteins belong to the premolten globule family of intrinsically disordered proteins. We suggest that the intrinsic disorder observed in the G0S2 protein may facilitate its interaction with multiple partners in the regulation of cellular metabolism.

更新日期：2020-10-13

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