Reassessing a sparse energetic network within a single protein domain.
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 286:295-299]. 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.
Chi
Celestine N
CN
Department of Medical Biochemistry and Microbiology, Uppsala University Biomedical Centre, Box 582, SE-751 23 Uppsala, Sweden.
Elfström
Lisa
L
Shi
Yao
Y
Snäll
Tord
T
Engström
Ake
A
Jemth
Per
P
D018360:Crystallography, X-Ray; D007700:Kinetics; D008024:Ligands; D050505:Mutant Proteins / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
D008024:Ligands; D050505:Mutant Proteins; D010455:Peptides; D011506:Proteins