Conservation of side-chain dynamics within a protein family.
The question of protein dynamics and its relevance to function is currently a topic of great interest. Proteins are particularly dynamic at the side-chain level on the time scale of picoseconds to nanoseconds. Here, we present a comparison of NMR-monitored side-chain motion between three PDZ domains of approximately 30% sequence identity and show that the side-chain dynamics display nontrivial conservation. Methyl (2)H relaxation was carried out to determine side-chain order parameters (S(2)), which were found to be more similar than naively expected from sequence, local packing, or a combination of the two. Thus, the dynamics of a rather distant homologue appears to be an excellent predictor of a protein's side-chain dynamics and, on average, better than current structure-based methods. Fast side-chain dynamics therefore display a high level of organization associated with global fold. Beyond simple conservation, the analysis herein suggests that the pattern of side-chain flexibility has significant contributions from nonlocal elements of the PDZ fold, such as correlated motions, and that the conserved dynamics may directly support function.
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Anthony B
AB
Law
Ernesto J
EJ
Fuentes
Andrew L
AL
Lee
D007700:Kinetics; D009038:Motion; D019906:Nuclear Magnetic Resonance, Biomolecular; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*
D011506:Proteins