Energetic pathway sampling in a protein interaction domain

Research output: Contribution to journalJournal articleResearchpeer-review

Greta Hultqvist, S. Raza Haq, Avinash S. Punekar, Celestine N. Chi, Ake Engström, Anders Bach, Kristian Strømgaard, Maria Selmer, Stefano Gianni, Per Jemth

The affinity and specificity of protein-ligand interactions are influenced by energetic crosstalk within the protein domain. However, the molecular details of such intradomain allostery are still unclear. Here, we have experimentally detected and computationally predicted interaction pathways 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.
Original languageEnglish
JournalStructure
Volume21
Issue number7
Pages (from-to)1193-1202
ISSN0969-2126
DOIs
Publication statusPublished - 25 Jun 2013

ID: 49468308