Abstract
The recognition of intrinsically disordered proteins (IDPs) is highly dependent on dynamics owing to the lack of structure. Here we studied the interplay between dynamics and molecular recognition in IDPs with a combination of time‐resolving tools on timescales ranging from femtoseconds to nanoseconds. We interrogated conformational dynamics and surface water dynamics and its attenuation upon partner binding using two IDPs, IBB and Nup153FG, both of central relevance to the nucleocytoplasmic transport machinery. These proteins bind the same nuclear transport receptor (Importinβ) with drastically different binding mechanisms, coupled folding–binding and fuzzy complex formation, respectively. Solvent fluctuations in the dynamic interface of the Nup153FG‐Importinβ fuzzy complex were largely unperturbed and slightly accelerated relative to the unbound state. In the IBB‐Importinβ complex, on the other hand, substantial relative slowdown of water dynamics was seen in a more rigid interface. These results show a correlation between interfacial water dynamics and the plasticity of IDP complexes, implicating functional relevance for such differential modulation in cellular processes, including nuclear transport.
Highlights
We studied the interplay between dynamics and molecular recognition in intrinsically disordered proteins (IDPs) with a combination of timeresolving tools on timescales ranging from femtoseconds to nanoseconds
In the IBBImportinb complex, on the other hand, substantial relative slowdown of water dynamics was seen in a more rigid interface. These results show a correlation between interfacial water dynamics and the plasticity of IDP complexes, implicating functional relevance for such differential modulation in cellular processes, including nuclear transport
Our results reveal differential dynamics in these systems across timescales ranging from femtoseconds to nanoseconds, and elucidate possible molecular underpinnings and functional relevance of mechanism-dependent differential IDP recognition
Summary
With an emphasis on solvation dynamics, here we directly interrogate the differential dynamics in two distinct IDP complexes formed via coupled folding–binding and fuzzy mechanisms using two disordered proteins, IBB and Nup153FG, both crucial players in nucleocytoplasmic transport.[5] Our results reveal differential dynamics in these systems across timescales ranging from femtoseconds to nanoseconds, and elucidate possible molecular underpinnings and functional relevance of mechanism-dependent differential IDP recognition. Both acrylodan-labeled IBB and Nup153FG in the free state showed bi-exponential relaxation behavior (Figure 2 D,E) with a nanosecond and sub-nanosecond component and some residual anisotropy.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
