caa a22 4500 606243062 CHVBK 20210128101322.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s12551-015-0162-x doi (NATIONALLICENCE)springer-10.1007/s12551-015-0162-x Nanoscale protein domain motion and long-range allostery in signaling proteins—a view from neutron spin echo spectroscopy [Elektronische Daten] [David Callaway, Zimei Bu] Many cellular proteins are multi-domain proteins. Coupled domain-domain interactions in these multidomain proteins are important for the allosteric relay of signals in the cellular signaling networks. We have initiated the application of neutron spin echo spectroscopy to the study of nanoscale protein domain motions on submicrosecond time scales and on nanometer length scale. Our NSE experiments reveal the activation of protein domain motions over a long distance of over more than 100Å in a multidomain scaffolding protein NHERF1 upon binding to another protein, Ezrin. Such activation of nanoscale protein domain motions is correlated with the allosteric assembly of multi-protein complexes by NHERF1 and Ezrin. Here, we summarize the theoretical framework that we have developed, which uses simple concepts from nonequilibrium statistical mechanics to interpret the NSE data, and employs a mobility tensor to describe nanoscale protein domain motion. Extracting nanoscale protein domain motion from the NSE does not require elaborate molecular dynamics simulations, nor complex fits to rotational motion, nor elastic network models. The approach is thus more robust than multiparameter techniques that require untestable assumptions. We also demonstrate that an experimental scheme of selective deuteration of a protein subunit in a complex can highlight and amplify specific domain dynamics from the abundant global translational and rotational motions in a protein. We expect NSE to provide a unique tool to determine nanoscale protein dynamics for the understanding of protein functions, such as how signals are propagated in a protein over a long distance to a distal domain. International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag Berlin Heidelberg, 2015 Protein domain dynamics nationallicence Neutron spin echo spectroscopy nationallicence Multidomain protein nationallicence Intrinsically disordered protein nationallicence Long-range allostery nationallicence Mobility tensor nationallicence Callaway David Department of Chemistry, The City College of New York, 10031, New York, NY, USA aut Bu Zimei Department of Chemistry, The City College of New York, 10031, New York, NY, USA aut Biophysical Reviews Springer Berlin Heidelberg 7/2(2015-06-01), 165-174 1867-2450 7:2<165 2015 7 12551 https://doi.org/10.1007/s12551-015-0162-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s12551-015-0162-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Callaway David Department of Chemistry, The City College of New York, 10031, New York, NY, USA aut NATIONALLICENCE 700 1- Bu Zimei Department of Chemistry, The City College of New York, 10031, New York, NY, USA aut NATIONALLICENCE 773 0- Biophysical Reviews Springer Berlin Heidelberg 7/2(2015-06-01), 165-174 1867-2450 7:2<165 2015 7 12551