Transport receptor occupancy in nuclear pore complex mimics

作     者：Alessio Fragasso Hendrik W.de Vries John Andersson Eli Ovan der Sluis Erik van der Giessen Patrick R.Onck Cees Dekker Alessio Fragasso;Hendrik W.de Vries;John Andersson;Eli O.van der Sluis;Erik van der Giessen;Patrick R.Onck;Cees Dekker

作者机构：Department of BionanoscienceKavli Institute of NanoscienceDelft University of TechnologyVan der Maasweg 9Delft 2629 HZThe Netherlands Zernike Institute for Advanced MaterialsUniversity of GroningenNijenborgh 4Groningen 9747AGThe Netherlands Department of Chemistry and Chemical EngineeringChalmers University of TechnologyKemivägen 10Gothenburg SE-41296Sweden 

出 版 物：《Nano Research》 (纳米研究（英文版）)

年 卷 期：2022年第15卷第11期

页      面：9689-9703页

核心收录：

学科分类：08[工学] 0805[工学-材料科学与工程（可授工学、理学学位）] 080502[工学-材料学] 0703[理学-化学] 0702[理学-物理学] 

基　　金：funded by NWO-I programme“Projectruimte” Grant No.16PR3242-1 

主　　题：nuclear pore complex intrinsically disordered proteins nuclear transport receptors karyopherins nanopores biomimetics molecular dynamics coarse-grained modeling 

摘      要：Nuclear pore complexes(NPCs)regulate all molecular transport between the nucleus and the cytoplasm in eukaryotic *** disordered Phe-Gly nucleoporins(FG-Nups)line the central conduit of NPCs to impart a selective barrier where large proteins are excluded unless bound to a transport receptor(karyopherin;Kap).Here,we assess“Kap-centricNPC models,which postulate that Kaps participate in establishing the selective *** combine biomimetic nanopores,formed by tethering Nsp1 to the inner wall of a solid-state nanopore,with coarse-grained modeling to show that yeast Kap95 exhibits two populations in Nsp1-coated pores:one population that is transported across the pore in milliseconds,and a second population that is stably assembled within the FG mesh of the *** current measurements show a conductance decrease for increasing Kap concentrations and noise data indicate an increase in rigidity of the *** reveals an accumulation of Kap95 near the pore wall,yielding a conductance *** find that Kaps only mildly affect the conformation of the Nsp1 mesh and that,even at high concentrations,Kaps only bind at most 8%of the FG-motifs in the nanopore,indicating that Kap95 occupancy is limited by steric constraints rather than by depletion of available *** data provide an alternative explanation of the origin of bimodal NPC binding of Kaps,where a stable population of Kaps binds avidly to the NPC periphery,while fast transport proceeds via a central FG-rich channel through lower affinity interactions between Kaps and the cohesive domains of Nsp1.