Rigidified Clicked Dimeric Ligands for Studying the Dynamics of the PDZ1-2 Supramodule of PSD-95
2015 (English)In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 16, no 1, 64-69 p.Article in journal (Refereed) Published
PSD-95 is a scaffolding protein of the MAGUK protein family, and engages in several vital protein-protein interactions in the brain with its PDZ domains. It has been suggested that PSD-95 is composed of two supramodules, one of which is the PDZ1-2 tandem domain. Here we have developed rigidified high-affinity dimeric ligands that target the PDZ1-2 supramodule, and established the biophysical parameters of the dynamic PDZ1-2/ligand interactions. By employing ITC, protein NMR, and stopped-flow kinetics this study provides a detailed insight into the overall conformational energetics of the interaction between dimeric ligands and tandem PDZ domains. Our findings expand our understanding of the dynamics of PSD-95 with potential relevance to its biological role in interacting with multivalent receptor complexes and development of novel drugs.
Place, publisher, year, edition, pages
2015. Vol. 16, no 1, 64-69 p.
dimeric ligands, NMR spectroscopy, PDZ domains, protein-protein interactions, PSD-95
Biological Sciences Chemical Sciences
IdentifiersURN: urn:nbn:se:uu:diva-242373DOI: 10.1002/cbic.201402547ISI: 000346781600009OAI: oai:DiVA.org:uu-242373DiVA: diva2:783605