Department of Biochemistry, University of Cambridge, 80, Tennis Court Road, Cambridge CB2 1GA, U.K.
Biochem Soc Trans. 2020 Dec 18;48(6):2669-2689. doi: 10.1042/BST20200467.
The structure-function paradigm has guided investigations into the molecules involved in cellular signalling for decades. The peripheries of this paradigm, however, start to unravel when considering the co-operation between proteins and the membrane in signalling processes. Intrinsically disordered regions hold distinct advantages over folded domains in terms of their binding promiscuity, sensitivity to their particular environment and their ease of modulation through post-translational modifications. Low sequence complexity and bias towards charged residues are also favourable for the multivalent electrostatic interactions that occur at the surfaces of lipid bilayers. This review looks at the principles behind the successful marriage between protein disorder and membranes in addition to the role of this partnership in modifying and regulating signalling in cellular processes. The HVR (hypervariable region) of small GTPases is highlighted as a well-studied example of the nuanced role a short intrinsically disordered region can play in the fine-tuning of signalling pathways.
结构-功能范式指导了数十年来细胞信号转导中涉及的分子的研究。然而，当考虑到蛋白质与膜在信号转导过程中的合作时，该范式的外围开始变得复杂。在结合的简并性、对其特定环境的敏感性以及通过翻译后修饰进行调节的容易性方面，无规卷曲区域具有比折叠结构域明显的优势。低序列复杂性和偏向带电荷残基也有利于脂质双层表面发生的多价静电相互作用。本综述探讨了蛋白质无序性与膜成功结合的背后原理，以及这种结合在修饰和调节细胞过程中的信号转导中的作用。小 GTP 酶的 HVR（高变区）被强调为一个很好的例子，说明了短的无规卷曲区域在精细调节信号通路方面可以发挥细微的作用。
