@article{1af87266311a4cd09aff69b220e95459,
title = "Deciphering the “Fuzzy” Interaction of FG Nucleoporins and Transport Factors Using Small-Angle Neutron Scattering",
abstract = "The largely intrinsically disordered phenylalanine-glycine-rich nucleoporins (FG Nups) underline a selectivity mechanism that enables the rapid translocation of transport factors (TFs) through the nuclear pore complexes (NPCs). Conflicting models of NPC transport have assumed that FG Nups undergo different conformational transitions upon interacting with TFs. To selectively characterize conformational changes in FG Nups induced by TFs we performed small-angle neutron scattering (SANS) with contrast matching. Conformational-ensembles derived from SANS data indicated an increase in the overall size of FG Nups is associated with TF interaction. Moreover, the organization of the FG motif in the interacting state is consistent with prior experimental analyses defining that FG motifs undergo conformational restriction upon interacting with TFs. These results provide structural insights into a highly dynamic interaction and illustrate how functional disorder imparts rapid and selective FG Nup-TF interactions. Sparks et al. use small-angle neutron scattering experiments to describe the fuzzy interactions between disordered FG Nups and transport factors (TFs) from the nuclear pore complex, thus elucidating the subtle conformational changes that TFs induce within FG Nup chains. The study helps to define “fuzziness” at intermediate length scales.",
keywords = "FG nucleoporins, Kap95, NTF2, contrast matching, ensemble analysis, intrinsically disordered proteins, nuclear pore complex, nuclear transport, small-angle neutron scattering, transport factors",
author = "Samuel Sparks and Temel, {Deniz B.} and Rout, {Michael P.} and David Cowburn",
note = "Funding Information: The authors thank Dr. Paul Dominic Olinares and Dr. Brian Chait for graciously providing mass spectrometry analysis and Drs. Barak Raveh and Ryo Hayama for their helpful discussion. Dr. Shuo Qian provided technical advice at ORNL. This work was supported by NIH GM117212 (D.C.) and GM112108 (M.R.). This research used resources at the High Flux Isotope Reactor, a DOE Office of Science User Facility operated by the Oak Ridge National Laboratory. Simulations used the Anton special-purpose supercomputer provided by the National Resource for Biomedical Supercomputing (NRBSC), the Pittsburgh Supercomputing Center (PSC), and the Biomedical Technology Research Center for Multiscale Modeling of Biological Systems (MMBioS) through grant P41GM103712-S1 from the NIH. D. E. Shaw Research generously made the Anton machine available. Simulations also used the XSEDE facilities supported by NSF ACI-105375. Funding Information: The authors thank Dr. Paul Dominic Olinares and Dr. Brian Chait for graciously providing mass spectrometry analysis and Drs. Barak Raveh and Ryo Hayama for their helpful discussion. Dr. Shuo Qian provided technical advice at ORNL. This work was supported by NIH GM117212 (D.C.) and GM112108 (M.R.). This research used resources at the High Flux Isotope Reactor , a DOE Office of Science User Facility operated by the Oak Ridge National Laboratory. Simulations used the Anton special-purpose supercomputer provided by the National Resource for Biomedical Supercomputing (NRBSC), the Pittsburgh Supercomputing Center (PSC), and the Biomedical Technology Research Center for Multiscale Modeling of Biological Systems (MMBioS) through grant P41GM103712-S1 from the NIH. D. E. Shaw Research generously made the Anton machine available. Simulations also used the XSEDE facilities supported by NSF ACI-105375 . Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",
year = "2018",
month = mar,
day = "6",
doi = "10.1016/j.str.2018.01.010",
language = "English (US)",
volume = "26",
pages = "477--484.e4",
journal = "Structure with Folding & design",
issn = "0969-2126",
publisher = "Cell Press",
number = "3",
}