A Programmable DNA origami platform for organizing intrinsically disordered nucleoporins within nanopore confinement

Fisher PDE, Shen Q, Akpinar B, Davis LK, Chung KKH, Baddeley D, Šarić A, Melia TJ, Hoogenboom BW, Lin C, Lusk CP. 2018. A Programmable DNA origami platform for organizing intrinsically disordered nucleoporins within nanopore confinement. ACS Nano. 12(2), 1508–1518.

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Author
Fisher, Patrick D. Ellis; Shen, Qi; Akpinar, Bernice; Davis, Luke K.; Chung, Kenny Kwok Hin; Baddeley, David; Šarić, AnđelaISTA ; Melia, Thomas J.; Hoogenboom, Bart W.; Lin, Chenxiang; Lusk, C. Patrick
Abstract
Nuclear pore complexes (NPCs) form gateways that control molecular exchange between the nucleus and the cytoplasm. They impose a diffusion barrier to macromolecules and enable the selective transport of nuclear transport receptors with bound cargo. The underlying mechanisms that establish these permeability properties remain to be fully elucidated but require unstructured nuclear pore proteins rich in Phe-Gly (FG)-repeat domains of different types, such as FxFG and GLFG. While physical modeling and in vitro approaches have provided a framework for explaining how the FG network contributes to the barrier and transport properties of the NPC, it remains unknown whether the number and/or the spatial positioning of different FG-domains along a cylindrical, ∼40 nm diameter transport channel contributes to their collective properties and function. To begin to answer these questions, we have used DNA origami to build a cylinder that mimics the dimensions of the central transport channel and can house a specified number of FG-domains at specific positions with easily tunable design parameters, such as grafting density and topology. We find the overall morphology of the FG-domain assemblies to be dependent on their chemical composition, determined by the type and density of FG-repeat, and on their architectural confinement provided by the DNA cylinder, largely consistent with here presented molecular dynamics simulations based on a coarse-grained polymer model. In addition, high-speed atomic force microscopy reveals local and reversible FG-domain condensation that transiently occludes the lumen of the DNA central channel mimics, suggestive of how the NPC might establish its permeability properties.
Publishing Year
Date Published
2018-01-19
Journal Title
ACS Nano
Acknowledgement
We thank J. Edel and members of the Lusk, Lin and Hoogenboom lab for discussion and acknowledge A. Pyne and R. Thorogate for support carrying out the AFM experiments. This work was funded by the NIH (R21GM109466 to CPL, CL and TJM, DP2GM114830 to CL, RO1GM105672 to CPL, and T32GM007223 to PDEF) and the UK Engineering and Physical Sciences Research Council (EP/L015277/1, EP/L504889/1, and EP/M028100/1).
Volume
12
Issue
2
Page
1508-1518
ISSN
eISSN
IST-REx-ID

Cite this

Fisher PDE, Shen Q, Akpinar B, et al. A Programmable DNA origami platform for organizing intrinsically disordered nucleoporins within nanopore confinement. ACS Nano. 2018;12(2):1508-1518. doi:10.1021/acsnano.7b08044
Fisher, P. D. E., Shen, Q., Akpinar, B., Davis, L. K., Chung, K. K. H., Baddeley, D., … Lusk, C. P. (2018). A Programmable DNA origami platform for organizing intrinsically disordered nucleoporins within nanopore confinement. ACS Nano. American Chemical Society. https://doi.org/10.1021/acsnano.7b08044
Fisher, Patrick D. Ellis, Qi Shen, Bernice Akpinar, Luke K. Davis, Kenny Kwok Hin Chung, David Baddeley, Anđela Šarić, et al. “A Programmable DNA Origami Platform for Organizing Intrinsically Disordered Nucleoporins within Nanopore Confinement.” ACS Nano. American Chemical Society, 2018. https://doi.org/10.1021/acsnano.7b08044.
P. D. E. Fisher et al., “A Programmable DNA origami platform for organizing intrinsically disordered nucleoporins within nanopore confinement,” ACS Nano, vol. 12, no. 2. American Chemical Society, pp. 1508–1518, 2018.
Fisher PDE, Shen Q, Akpinar B, Davis LK, Chung KKH, Baddeley D, Šarić A, Melia TJ, Hoogenboom BW, Lin C, Lusk CP. 2018. A Programmable DNA origami platform for organizing intrinsically disordered nucleoporins within nanopore confinement. ACS Nano. 12(2), 1508–1518.
Fisher, Patrick D. Ellis, et al. “A Programmable DNA Origami Platform for Organizing Intrinsically Disordered Nucleoporins within Nanopore Confinement.” ACS Nano, vol. 12, no. 2, American Chemical Society, 2018, pp. 1508–18, doi:10.1021/acsnano.7b08044.

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