RT Journal Article
SR Electronic
T1 Molecular model of the nuclear pore complex reveals a thermoreversible FG-network with distinct territories occupied by different FG motifs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 568865
DO 10.1101/568865
A1 Kai Huang
A1 Mario Tagliazucchi
A1 Sung Hyun Park
A1 Yitzhak Rabin
A1 Igal Szleifer
YR 2019
UL http://biorxiv.org/content/early/2019/03/05/568865.abstract
AB Despite the intensive study of the nuclear pore complex (NPC), its functional core, the central transporter, remains poorly understood. Here, we investigate this unfolded and dynamic part of the NPC using a molecular theory that addresses both entropic and enthalpic effects of the intrinsically disordered phenylalanine-glycine-rich nucleoporins (FG-Nups). Our model shows that the cooperative effect of FG-pairing, specific spacer cohesion, and charge interaction leads to a remarkably elaborate gating structure inside the NPC. In particular, we find sequence-programmed “phase separation” between charge-rich and charge-poor regions, and a polarized electrostatic potential throughout the NPC. The model predicts a thermoreversible FG-network with inhomogeneous FG-pairing fraction in space, which features distinct territories of different types of FG motifs. Our theoretical anatomy of the central transporter reveals a clear sequence-structure-function relationship of the FG-Nups, and explains in a self-consistent way how nucleocytoplasmic transport can be efficient yet specific.