Converging on the function of intrinsically disordered nucleoporins in the nuclear pore complex.
Several biological mechanisms involve proteins or proteinaceous components that are intrinsically disordered. A case in point pertains to the nuclear pore complex (NPC), which regulates molecular transport between the nucleus and the cytoplasm. NPC functionality is dependent on unfolded domains rich in Phe-Gly (FG) repeats (i.e., FG-domains) that collectively act to promote or hinder cargo translocation. To a large extent, our understanding of FG-domain behavior is limited to in vitro investigations given the difficulty to resolve them directly in the NPC. Nevertheless, recent findings indicate a collective convergence towards rationalizing FG-domain function. This review aims to glean further insight into this fascinating problem by taking an objective look at the boundary conditions and contextual details underpinning FG-domain behavior in the NPC. Here, we treat the FG-domains as being commensurate with polymeric chains to address ambiguities such as for instance, how FG-domains tethered to the central channel of the NPC would behave differently as compared with their free-floating counterparts in solution. By bringing such fundamental questions to the fore, this review seeks to illuminate the importance of how such parameters can hold influence over the structure-function relation of intrinsically disordered proteins in the NPC and beyond.
Peleg
Orit
O
Department of Materials, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
Lim
Roderick Y H
RY
D022022:Nuclear Pore / Q000737:chemistry / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000378:metabolism*; D020080:Tandem Repeat Sequences
D028861:Nuclear Pore Complex Proteins