Cooperative Interactions between Different Classes of Disordered Proteins Play a Functional Role in the Nuclear Pore Complex of Baker’s Yeast

Ando, David; Gopinathan, Ajay; Espinoza-Fonseca, L. Michel

doi:10.1371/journal.pone.0169455

Cooperative Interactions between Different Classes of Disordered Proteins Play a Functional Role in the Nuclear Pore Complex of Baker’s Yeast

Journal Article · Mon Jan 09 00:00:00 EST 2017 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0169455· OSTI ID:1627813

Ando, David ^[1]; Gopinathan, Ajay ^[2]; Espinoza-Fonseca, L. Michel ^[3]

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences Division; Joint BioEnergy Institute, Emeryville, CA (United States); DOE/OSTI
Univ. of California, Merced, CA (United States). Dept., of Physics
Univ. of Minnesota, Twin Cities (United States)

Nucleocytoplasmic transport is highly selective, efficient, and is regulated by a poorly understood mechanism involving hundreds of disordered FG nucleoporin proteins (FG nups) lining the inside wall of the nuclear pore complex (NPC). Previous research has concluded that FG nups in Baker’s yeast (S. cerevisiae) are present in a bimodal distribution, with the “Forest Model” classifying FG nups as either di-block polymer like “trees” or single-block polymer like “shrubs”. Using a combination of coarse-grained modeling and polymer brush modeling, the function of the di-block FG nups has previously been hypothesized in the Di-block Copolymer Brush Gate (DCBG) model to form a higher-order polymer brush architecture which can open and close to regulate transport across the NPC. In this manuscript we work to extend the original DCBG model by first performing coarse grained simulations of the single-block FG nups which confirm that they have a single block polymer structure rather than the di-block structure of tree nups. Our molecular simulations also demonstrate that these single-block FG nups are likely cohesive, compact, collapsed coil polymers, implying that these FG nups are generally localized to their grafting location within the NPC. We find that adding a layer of single-block FG nups to the DCBG model increases the range of cargo sizes which are able to translocate the pore through a cooperative effect involving single-block and di-block FG nups. This effect can explain the puzzling connection between single-block FG nup deletion mutants in S. cerevisiae and the resulting failure of certain large cargo transport through the NPC. Facilitation of large cargo transport via single-block and di-block FG nup cooperativity in the nuclear pore could provide a model mechanism for designing future biomimetic pores of greater applicability.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1627813

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 1 Vol. 12; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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Data from: Cooperative interactions between different classes of disordered proteins play a functional role in the nuclear pore complex of Baker's yeast Ando, David E.; Gopinathan, Ajay; Ando, David Dryad https://doi.org/10.5061/dryad.4663t	dataset	January 2017
Transport of probe particles in a polymer network: effects of probe size, network rigidity and probe–polymer interaction Kumar, Praveen; Theeyancheri, Ligesh; Chaki, Subhasish Soft Matter, Vol. 15, Issue 44 https://doi.org/10.1039/c9sm01822k	journal	January 2019
Interactions between a fluctuating polymer barrier and transport factors together with enzyme action are sufficient for selective and rapid transport through the nuclear pore complex Ro, Sunghan; Gopinathan, Ajay; Kim, Yong Woon Physical Review E, Vol. 98, Issue 1 https://doi.org/10.1103/physreve.98.012403	journal	July 2018

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