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Conservation of side-chain dynamics within a protein family
Journal article

Conservation of side-chain dynamics within a protein family

Anthony B Law, Ernesto J Fuentes and Andrew L Lee
Journal of the American Chemical Society, Vol.131(18), pp.6322-6323
05/13/2009
DOI: 10.1021/ja809915a
PMCID: PMC2678171
PMID: 19374353
url
http://doi.org/10.1021/ja809915aView
Open Access

Abstract

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.
Protein Structure, Tertiary Nuclear Magnetic Resonance, Biomolecular Motion Kinetics Proteins - chemistry

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