A designer FG-Nup that reconstitutes the selective transport barrier of the nuclear pore complex
Artikel i vetenskaplig tidskrift, 2021

Nuclear Pore Complexes (NPCs) regulate bidirectional transport between the nucleus and the cytoplasm. Intrinsically disordered FG-Nups line the NPC lumen and form a selective barrier, where transport of most proteins is inhibited whereas specific transporter proteins freely pass. The mechanism underlying selective transport through the NPC is still debated. Here, we reconstitute the selective behaviour of the NPC bottom-up by introducing a rationally designed artificial FG-Nup that mimics natural Nups. Using QCM-D, we measure selective binding of the artificial FG-Nup brushes to the transport receptor Kap95 over cytosolic proteins such as BSA. Solid-state nanopores with the artificial FG-Nups lining their inner walls support fast translocation of Kap95 while blocking BSA, thus demonstrating selectivity. Coarse-grained molecular dynamics simulations highlight the formation of a selective meshwork with densities comparable to native NPCs. Our findings show that simple design rules can recapitulate the selective behaviour of native FG-Nups and demonstrate that no specific spacer sequence nor a spatial segregation of different FG-motif types are needed to create selective NPCs.

Författare

Alessio Fragasso

TU Delft

Hendrik W. de Vries

Rijksuniversiteit Groningen

John Andersson

Chalmers, Kemi och kemiteknik, Tillämpad kemi, Andreas Dahlin Group

Eli O. van der Sluis

TU Delft

Erik van der Giessen

Rijksuniversiteit Groningen

Andreas Dahlin

Chalmers, Kemi och kemiteknik, Tillämpad kemi, Andreas Dahlin Group

Patrick R. Onck

Rijksuniversiteit Groningen

C. Dekker

TU Delft

Nature Communications

2041-1723 (ISSN)

Vol. 12 1 2010- 2010

Ämneskategorier

Biokemi och molekylärbiologi

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

Läkemedelskemi

Styrkeområden

Hälsa och teknik

Infrastruktur

Chalmers materialanalyslaboratorium

DOI

10.1038/s41467-021-22293-y

PubMed

33790297

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Senast uppdaterat

2021-05-11