Evaluation of Energetic and Dynamic Coupling Networks in a PDZ Domain Protein

  • Fuentes E
  • Gilmore S
  • Mauldin R
 et al. 
  • 69


    Mendeley users who have this article in their library.
  • 75


    Citations of this article.


A number of computational and experimental studies have identified intramolecular communication "pathways" or "networks" important for transmitting allostery. Here, we have used mutagenesis and NMR relaxation methods to investigate the scope and nature of the communication networks found in the second post-synaptic density-95/discs large/zonula occludens-1 (PDZ) domain of the human protein tyrosine phosphatase 1E protein (hPTP1E) (PDZ2). It was found that most mutations do not have a significant energetic contribution to peptide ligand binding. Three mutants that showed significant changes in binding also displayed context-dependent dynamic effects. Both a mutation at a partially exposed site (H71Y) and a buried core position (I35V) had a limited response in side-chain2H-based dynamics when compared to wild-type PDZ2. In contrast, a change at a second core position (I20F) that had previously been shown to be part of an energetic and dynamic network, resulted in extensive changes in side-chain dynamics. This response is reminiscent to that seen previously upon peptide ligand binding. These results shed light on the nature of the PDZ2 dynamic network and suggest that position 20 in PDZ2 acts as a "hub" that is energetically and dynamically critical for transmitting changes in dynamics throughout the PDZ domain. © 2006 Elsevier Ltd. All rights reserved.

Author-supplied keywords

  • PDZ domain
  • allostery
  • dynamic coupling
  • protein dynamics
  • protein-protein interaction

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Ernesto J. Fuentes

  • Steven A. Gilmore

  • Randall V. Mauldin

  • Andrew L. Lee

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free