Clogging-free transport by the crowded Nuclear Pore Complex

by Prof. Anton Zilman

Physics Department and Department of Biomedical Engineering University of Toronto

at Biological and soft-matter physics

Thu, 28 Dec 2023, 12:10
SPECIAL seminar, Sacta-Rashi Building for Physics (54), room 207

Abstract

The nuclear pore complex (NPC) is the main conduit for transporting materials into and out of the nucleus of eukaryotic cells. The channel of the NPC is occupied by an assembly of intrinsically disordered proteins (IDPs), serving as a main component of the NPC's transport mechanism dictating its specificity and throughput. These IDPs – that to a large extent can be understood as flexible self-associating polymers – set up permeability barrier and serve as a template for the binding of the cargo-carrying transport proteins. NPC transport channel is a highly crowded environment occupied by the large numbers of simultaneously translocating cargo-carrying and free transport proteins traveling in both directions. How the NPC can efficiently, rapidly and selectively transport cargoes without clogging remains ill understood. Past experimental results suggest that the NPC is surprisingly resistant to clogging and that the accumulation of cargoes inside the pore can even result in faster and more efficient transport. To understand the mechanisms behind these puzzling observations and investigate existing hypotheses, we have constructed a computational model of the NPC comprising only a minimal set of features. This model explains the previous experimental results and pinpoints the mechanisms which produce this robust response to crowding arising from nonlinear conformational dynamics of the IDPs in the pore. Some of these mechanisms are universal and pertain to a broad class of selective transport nanopores. On top of these universal mechanisms, the particular spatial architecture of the IDP assembly in the NPC channel endows it with the counter-intuitive ability to leverage crowding to achieve faster and more efficient bi-directional transport.

Created on 17-12-2023 by Granek, Rony (rgranek)
Updaded on 30-12-2023 by Granek, Rony (rgranek)