Manjunath G P, Ramanujam Praveena L, Galande Sanjeev
Indian Institute of Science Education and Research, Pune 411 008, India.
J Biosci. 2018 Mar;43(1):155-171.
Protein scaffolds as essential backbones for organization of supramolecular signalling complexes are a recurrent theme in several model systems. Scaffold proteins preferentially employ linear peptide binding motifs for recruiting their interaction partners. PDZ domains are one of the more commonly encountered peptide binding domains in several proteins including those involved in scaffolding functions. This domain is known for its promiscuity both in terms of ligand selection, mode of interaction with its ligands as well as its association with other protein interaction domains. PDZ domains are subject to several means of regulations by virtue of their functional diversity. Additionally, the PDZ domains are refractive to the effect of mutations and maintain their three-dimensional architecture under extreme mutational load. The biochemical and biophysical basis for this selectivity as well as promiscuity has been investigated and reviewed extensively. The present review focuses on the plasticity inherent in PDZ domains and its implications for modular organization as well as evolution of cellular signalling pathways in higher eukaryotes.
蛋白质支架作为超分子信号复合物组织的基本骨架，是多个模型系统中反复出现的主题。支架蛋白优先利用线性肽结合基序来招募其相互作用伙伴。PDZ结构域是几种蛋白质中较为常见的肽结合结构域之一，包括那些参与支架功能的蛋白质。该结构域因其在配体选择、与配体的相互作用模式以及与其他蛋白质相互作用结构域的关联方面的混杂性而闻名。由于其功能多样性，PDZ结构域受到多种调控方式的影响。此外，PDZ结构域对突变的影响具有抗性，并在极端突变负荷下维持其三维结构。这种选择性以及混杂性的生化和生物物理基础已得到广泛研究和综述。本综述重点关注PDZ结构域固有的可塑性及其对高等真核生物中模块化组织以及细胞信号通路进化的影响。
