Two differential binding mechanisms of FG-nucleoporins and nuclear transport receptors

Journal article

Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC). Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs. Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1. Association and dissociation rate constants are more than an order of magnitude lower than in the archetypal-fuzzy complex between FG-Nup153 and NTRs. Unexpectedly, this behavior appears not to be encoded selectively into CRM1 but rather into the FG-Nup214 sequence. The same distinct binding mechanisms are unperturbed in O-linked β-N-acetylglucosamine-modified FG-Nups. Our results have implications for differential roles of distinctly spatially distributed FG-Nup⋅NTR interactions in the cell.

Authors: Tan, P; Aramburu, I; Mercadante, D; Tyagi, S; Chowdhury, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Cell Reports
• Volume: 22
• Issue: 13
• Pages: 3660-3671
• Publication date: 2018-03-27
• Acceptance date: 2018-03-06
• DOI: 10.1016/j.celrep.2018.03.022
• EISSN: 2211-1247
• ISSN: 2211-1247
• Pmid: 29590630
• Language: English
• Keywords: FG-Nup; molecular dynamics simulations; nuclear transport receptors; intrinsically disordered protein; binding mechanism; single-molecule FRET; glycosylation