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Nanoscale protein domain motion and long-range allostery in signaling proteins- a view from neutron spin echo sprectroscopy.

ABSTRACT: 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 100 Å in a multidomain scaffolding protein NHERF1 upon binding to another protein Ezrin. Such activation of nanoscale protein domains 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, or complex fits to rotational motion, or 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.

SUBMITTER: Callaway DJ

PROVIDER: S-EPMC4438997 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Activation of nanoscale allosteric protein domain motion revealed by neutron spin echo spectroscopy.

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