Abstract
Recent studies show that neutron spin echo spectroscopy (NSE) can reveal long-range protein domain motions on nanometer lengthscales and on nanosecond to microsecond timescales. This unique capability of NSE provides new opportunities to understand protein dynamics and functions, such as how binding signals are propagated in a protein to distal sites. Here we review our applications of NSE to the study of nanoscale protein domain motions in a set of cell signaling proteins. We summarize the theoretical framework we have developed, which allows one to interpret the NSE data (Biophys. J. 99, 3473 (2010) and Proc. Natl. Acad. Sci. USA 102, 17646 (2005)). Our theoretical framework uses simple concepts from nonequilibrium statistical mechanics, and does not require elaborate molecular dynamics simulations, complex fits to rotational motion, or elastic network models. It is thus more robust than multiparameter techniques that require untestable assumptions. We also demonstrate our experimental scheme involving deuterium labeling of a protein domain or a subunit in a protein complex. We show that our selective deuteration scheme can highlight and resolve specific domain dynamics from the abundant global translational and rotational motions in a protein. Our approach thus clears significant hurdles to the application of NSE for the study of protein dynamics in solution.
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Contribution to the Topical Issue “Neutron Biological Physics”, edited by Giovanna Fragneto and Frank Gabel.
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Callaway, D.J.E., Farago, B. & Bu, Z. Nanoscale protein dynamics: A new frontier for neutron spin echo spectroscopy. Eur. Phys. J. E 36, 76 (2013). https://doi.org/10.1140/epje/i2013-13076-1
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DOI: https://doi.org/10.1140/epje/i2013-13076-1