Murciano-Calles Javier
Departamento de Química Física, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain.
Life (Basel). 2020 Jul 27;10(8):123. doi: 10.3390/life10080123.
The PDZ domain (PSD95-Discs large-ZO1) is a widespread modular domain present in the living organisms. A prevalent function in the PDZ family is to serve as scaffolding and adaptor proteins connecting multiple partners in signaling pathways. An explanation of the flexible functionality in this domain family, based just on a static perspective of the structure-activity relationship, might fall short. More dynamic and conformational aspects in the protein fold can be the reasons for such functionality. Folding studies indeed showed an ample and malleable folding landscape for PDZ domains where multiple intermediate states were experimentally detected. Allosteric phenomena that resemble energetic coupling between residues have also been found in PDZ domains. Additionally, several PDZ domains are modulated by post-translational modifications, which introduce conformational switches that affect binding. Altogether, the ability to connect diverse partners might arise from the intrinsic plasticity of the PDZ fold.
PDZ结构域（PSD95-盘状大蛋白-ZO1）是存在于生物体内的一种广泛分布的模块化结构域。PDZ家族的一个普遍功能是作为支架蛋白和衔接蛋白，在信号通路中连接多个相互作用分子。仅基于结构-活性关系的静态观点来解释该结构域家族的灵活功能，可能并不充分。蛋白质折叠中更具动态性和构象方面的因素可能是产生这种功能的原因。折叠研究确实表明，PDZ结构域具有丰富且可塑性强的折叠态势，实验检测到了多个中间状态。在PDZ结构域中还发现了类似于残基间能量耦合的别构现象。此外，几种PDZ结构域受到翻译后修饰的调控，这些修饰会引入影响结合的构象转换。总之，连接不同相互作用分子的能力可能源于PDZ折叠的内在可塑性。
