Erlendsson Simon, Madsen Kenneth Lindegaard
Molecular Neuropharmacology Laboratory, Lundbeck Foundation Center for Biomembranes in Nanomedicine, Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, The Panum Institute 18.6, University of Copenhagen, Copenhagen N 2200, Denmark.
Membranes (Basel). 2015 Oct 16;5(4):597-615. doi: 10.3390/membranes5040597.
Scaffolding proteins serve to assemble protein complexes in dynamic processes by means of specific protein-protein and protein-lipid binding domains. Many of these domains bind either proteins or lipids exclusively; however, it has become increasingly evident that certain domains are capable of binding both. Especially, many PDZ domains, which are highly abundant protein-protein binding domains, bind lipids and membranes. Here we provide an overview of recent large-scale studies trying to generalize and rationalize the binding patterns as well as specificity of PDZ domains towards membrane lipids. Moreover, we review how these PDZ-membrane interactions are regulated in the case of the synaptic scaffolding protein PICK1 and how this might affect cellular localization and function.
支架蛋白通过特定的蛋白质-蛋白质和蛋白质-脂质结合结构域，在动态过程中组装蛋白质复合物。这些结构域中的许多仅与蛋白质或脂质结合；然而，越来越明显的是，某些结构域能够同时结合两者。特别是，许多PDZ结构域是高度丰富的蛋白质-蛋白质结合结构域，它们能结合脂质和膜。在这里，我们概述了最近的大规模研究，这些研究试图归纳和合理化PDZ结构域与膜脂的结合模式以及特异性。此外，我们还综述了在突触支架蛋白PICK1的情况下，这些PDZ-膜相互作用是如何被调控的，以及这可能如何影响细胞定位和功能。
