Conservation of Side-Chain Dynamics Within a Protein Family

• Published in: Journal of the American Chemical Society 2009-05, Vol.131 (18), p.6322-6323
• Main Authors: Law, Anthony B, Fuentes, Ernesto J, Lee, Andrew L
• Format: Article
• Language: English
• Subjects: Kinetics; Motion; Nuclear Magnetic Resonance, Biomolecular; Protein Structure, Tertiary; Proteins - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja809915a

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 ∼30% sequence identity and show that the side-chain dynamics display nontrivial conservation. Methyl 2H 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.