Abstract

Understanding the molecular principles that govern allosteric communication is an important goal in protein science. One way allostery could be transmitted is via sparse energetic networks of residues, and one such evolutionary conserved network was identified in the PDZ domain family of proteins by multiple sequence alignment [Lockless SW, Ranganathan R (1999) Science 286:295299]. We have reassessed the energetic coupling of these residues by double mutant cycles together with ligand binding and stability experiments and found that coupling is not a special property of the coevolved network of residues in PDZ domains. The observed coupling for ligand binding is better explained by a distance relationship, where residues close in space are more likely to couple than distal residues. Our study demonstrates that statistical coupling from sequence analysis is not necessarily a reporter of energetic coupling and allostery.

Keywords

allostery; coupling energy; dynamics; energetic network of residues; PDZ domain

Published in

Proceedings of the National Academy of Sciences
2008, Volume: 105, number: 12, pages: 4679-4684
Publisher: NATL ACAD SCIENCES

SLU Authors

• Snäll, Tord

  • Department of Ecology, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Microbiology


Publication identifier

DOI: https://doi.org/10.1073/pnas.0711732105

Permanent link to this page (URI)

https://res.slu.se/id/publ/17715