---
_id: '10362'
abstract:
- lang: eng
text: 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.
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).
article_processing_charge: No
article_type: original
author:
- first_name: Patrick D. Ellis
full_name: Fisher, Patrick D. Ellis
last_name: Fisher
- first_name: Qi
full_name: Shen, Qi
last_name: Shen
- first_name: Bernice
full_name: Akpinar, Bernice
last_name: Akpinar
- first_name: Luke K.
full_name: Davis, Luke K.
last_name: Davis
- first_name: Kenny Kwok Hin
full_name: Chung, Kenny Kwok Hin
last_name: Chung
- first_name: David
full_name: Baddeley, David
last_name: Baddeley
- first_name: Anđela
full_name: Šarić, Anđela
id: bf63d406-f056-11eb-b41d-f263a6566d8b
last_name: Šarić
orcid: 0000-0002-7854-2139
- first_name: Thomas J.
full_name: Melia, Thomas J.
last_name: Melia
- first_name: Bart W.
full_name: Hoogenboom, Bart W.
last_name: Hoogenboom
- first_name: Chenxiang
full_name: Lin, Chenxiang
last_name: Lin
- first_name: C. Patrick
full_name: Lusk, C. Patrick
last_name: Lusk
citation:
ama: 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
apa: 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
chicago: 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.
ieee: 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.
ista: 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.
mla: 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.
short: P.D.E. Fisher, Q. Shen, B. Akpinar, L.K. Davis, K.K.H. Chung, D. Baddeley,
A. Šarić, T.J. Melia, B.W. Hoogenboom, C. Lin, C.P. Lusk, ACS Nano 12 (2018) 1508–1518.
date_created: 2021-11-26T15:15:00Z
date_published: 2018-01-19T00:00:00Z
date_updated: 2021-11-26T15:57:02Z
day: '19'
doi: 10.1021/acsnano.7b08044
extern: '1'
external_id:
pmid:
- '29350911'
intvolume: ' 12'
issue: '2'
keyword:
- general physics and astronomy
language:
- iso: eng
month: '01'
oa_version: None
page: 1508-1518
pmid: 1
publication: ACS Nano
publication_identifier:
eissn:
- 1936-086X
issn:
- 1936-0851
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: A Programmable DNA origami platform for organizing intrinsically disordered
nucleoporins within nanopore confinement
type: journal_article
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
volume: 12
year: '2018'
...