NMR Research Today is a free monthly online journal that collates and summarizes the latest research about NMR, including details on nuclear magnetic resonance, structural determination, techniques.

Propagation of dynamic changes in barnase upon binding of barstar: an NMR and computational study.

Zhuravleva A, Korzhnev DM, Nolde SB, Kay LE, Arseniev AS, Billeter M, Orekhov VY

Swedish NMR Centre at Göteborg University, Box 465, 405 30 Göteborg, Sweden.

NMR spectroscopy and computer simulations were used to examine changes in chemical shifts and in dynamics of the ribonuclease barnase that result upon binding to its natural inhibitor barstar. Although the spatial structures of free and bound barnase are very similar, binding results in changes of the dynamics of both fast side-chains, as revealed by (2)H relaxation measurements, and NMR chemical shifts in an extended beta-sheet that is located far from the binding interface. Both side-chain dynamics and chemical shifts are sensitive to variations in the ensemble populations of the inter-converting molecular states, which can escape direct structural observation. Molecular dynamics simulations of free barnase and barnase in complex with barstar, as well as a normal mode analysis of barnase using a Gaussian network model, reveal relatively rigid domains that are separated by the extended beta-sheet mentioned above. The observed changes in NMR parameters upon ligation can thus be rationalized in terms of changes in inter-domain dynamics and in populations of exchanging states, without measurable structural changes. This provides an alternative model for the propagation of a molecular response to ligand binding across a protein that is based exclusively on changes in dynamics.

Published 19 March 2007 in J Mol Biol, 367(4): 1079-92.
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