The intrinsically disordered N-terminal domains of the Src family kinases are responsible for driving membrane association. Despite the importance of these processes in controlling subcellular and spatial localization, little is known about the structural details of the protein-membrane interactions. Focusing on the SH4 and Unique domains of the Src family kinase member Hck, we present a new methodology for using neutron reflectometry and solution state nuclear magnetic resonance data to restrain molecular dynamics simulations and produce a first of its kind atomically detailed ensemble of structures of a membrane bound intrinsically disordered protein. The consistency of the model with available experimental data prompted the combination of the ensemble with structures of the regulatory and catalytic domains generated from SAXS to generate the first full-length models of membrane bound Hck.<br/>

Structural characterization of Hck-membrane association based on the analysis of neutron reflectometry and solution NMR data with restrained-ensemble molecular dynamics simulations

2019 Spring National Meeting

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