Post-translational modifications modulate ligand recognition by the third PDZ domain of the MAGUK protein PSD-95.

ABSTRACT: The relative promiscuity of hub proteins such as postsynaptic density protein-95 (PSD-95) can be achieved by alternative splicing, allosteric regulation, and post-translational modifications, the latter of which is the most efficient method of accelerating cellular responses to environmental changes in vivo. Here, a mutational approach was used to determine the impact of phosphorylation and succinimidation post-translational modifications on the binding affinity of the postsynaptic density protein-95/discs large/zonula occludens-1 (PDZ3) domain of PSD-95. Molecular dynamics simulations revealed that the binding affinity of this domain is influenced by an interplay between salt-bridges linking the α3 helix, the β2-β3 loop and the positively charged Lys residues in its high-affinity hexapept

SUBMITTER: Murciano-Calles J 

PROVIDER: S-EPMC3935999 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature