PDZ (PSD-95/Dlg/Zo-1) domains are small, structurally conserved protein-protein interaction modules (~90 amino acids), which consist of six beta-strands and two alpha-helices. They are highly represented in the human proteome and regulate the spatial and temporal function of proteins or signaling complexes, such as synaptic transmembrane and cell adhesion proteins. PDZ domains selectively interact with linear peptide motifs known as PDZ-binding-motifs (PBMs) of their binding partner proteins and mutations are associated with several human disorders. In this seminar, I will present recent work on understanding PDZ domain specificity with respect to individual structural positions that form the binding pocket to connect sequence, structure, dynamics, and function in a general context. Two distinct types of PBMs will be discussed – C-terminal PBMs and internal PBMs. In addition, initial steps in designing de novo PDZ domains for engineering specificity will be presented. Collectively, these studies show promise for the design of artificial PDZ domains with engineered specificities.
https://medicine.uiowa.edu/biochemistry-molecular-biology/profile/ernesto-fuentes