Natively Unfolded FG Repeats Stabilize the Structure of the Nuclear Pore Complex

TY - JOUR

T1 - Natively Unfolded FG Repeats Stabilize the Structure of the Nuclear Pore Complex

AU - Onischenko, Evgeny

AU - Tang, Jeffrey H

AU - Andersen, Kasper R

AU - Knockenhauer, Kevin E

AU - Vallotton, Pascal

AU - Derrer, Carina P

AU - Kralt, Annemarie

AU - Mugler, Christopher F

AU - Chan, Leon Y

AU - Schwartz, Thomas U

AU - Weis, Karsten

N1 - Copyright © 2017 Elsevier Inc. All rights reserved.

PY - 2017/11/2

Y1 - 2017/11/2

N2 - Nuclear pore complexes (NPCs) are ∼100 MDa transport channels assembled from multiple copies of ∼30 nucleoporins (Nups). One-third of these Nups contain phenylalanine-glycine (FG)-rich repeats, forming a diffusion barrier, which is selectively permeable for nuclear transport receptors that interact with these repeats. Here, we identify an additional function of FG repeats in the structure and biogenesis of the yeast NPC. We demonstrate that GLFG-containing FG repeats directly bind to multiple scaffold Nups in vitro and act as NPC-targeting determinants in vivo. Furthermore, we show that the GLFG repeats of Nup116 function in a redundant manner with Nup188, a nonessential scaffold Nup, to stabilize critical interactions within the NPC scaffold needed for late steps of NPC assembly. Our results reveal a previously unanticipated structural role for natively unfolded GLFG repeats as Velcro to link NPC subcomplexes and thus add a new layer of connections to current models of the NPC architecture. In addition to forming the permeability barrier, FG repeats in nucleoporins contribute structurally to nuclear pore biogenesis and function.

AB - Nuclear pore complexes (NPCs) are ∼100 MDa transport channels assembled from multiple copies of ∼30 nucleoporins (Nups). One-third of these Nups contain phenylalanine-glycine (FG)-rich repeats, forming a diffusion barrier, which is selectively permeable for nuclear transport receptors that interact with these repeats. Here, we identify an additional function of FG repeats in the structure and biogenesis of the yeast NPC. We demonstrate that GLFG-containing FG repeats directly bind to multiple scaffold Nups in vitro and act as NPC-targeting determinants in vivo. Furthermore, we show that the GLFG repeats of Nup116 function in a redundant manner with Nup188, a nonessential scaffold Nup, to stabilize critical interactions within the NPC scaffold needed for late steps of NPC assembly. Our results reveal a previously unanticipated structural role for natively unfolded GLFG repeats as Velcro to link NPC subcomplexes and thus add a new layer of connections to current models of the NPC architecture. In addition to forming the permeability barrier, FG repeats in nucleoporins contribute structurally to nuclear pore biogenesis and function.

KW - Journal Article

UR - http://www.scopus.com/inward/record.url?scp=85031295921&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2017.09.033

DO - 10.1016/j.cell.2017.09.033

M3 - Journal article

C2 - 29033133

SN - 0092-8674

VL - 171

SP - 904

EP - 917

JO - Cell

JF - Cell

IS - 4

ER -