Energetic pathway sampling in a protein interaction domain
2013 (English)In: Structure, ISSN 0969-2126, E-ISSN 1878-4186, Vol. 21, 1193-1202 p.Article in journal (Other academic) Published
The affinity and specificity of protein-ligand interactions are influenced by energeticcrosstalk within the protein domain. However, the molecular details of such intradomain allostery are still unclear. Here, we have experimentally detected and computationally predicted interactionpathways in the postsynaptic density 95/discs large/zonula occludens 1 (PDZ)-peptide ligand model system using wild-type and circularly permuted PDZ proteins. The circular permutant introduced small perturbations in the tertiary structure and a concomitant rewiring of allosteric pathways, allowing us to describe how subtle changes may reshape energetic signaling. The results were analyzed in the context of other members of the PDZ family, which were found to contain distinct interaction pathways for different peptide ligands. The data reveal a fascinating scenario whereby several energetic pathways are sampled within one single domain and distinct pathways are activated by specific protein ligands.
Place, publisher, year, edition, pages
2013. Vol. 21, 1193-1202 p.
intradomain allostery, PDZ domain, protein binding, circular permutant
Biochemistry and Molecular Biology
Research subject Biochemistry
IdentifiersURN: urn:nbn:se:uu:diva-185579DOI: 10.1016/j.str.2013.05.010ISI: 000321681600016OAI: oai:DiVA.org:uu-185579DiVA: diva2:575639