Structure function relations in PDZ-domain-containing proteins: Implications for protein networks in cellular signalling

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.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Biological Evolution
  • Conserved Sequence
  • Humans
  • Ligands
  • PDZ Domains*
  • Protein Binding
  • Protein Interaction Domains and Motifs*
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Synapses / metabolism


  • Ligands
  • Proteins