Disordered Motifs and Domains in Cell Control
Poster Session II
30-POS
Board 6
Disordered FG-repeat Domains in the Nuclear Pore Complex
Mohammad R. Mofrad
.
University of California, Berkeley, CA, USA.
Motivation: Disordered FG-repeat domains coat the inner layer of the nuclear pore complex
(NPC) and are believed to play a central role in the selectivity barrier function of the NPC,
exclusively controlling the vital traffic of macromolecules into and out of the nucleus [1]. The
confinement of the FG-repeat domains to the central channel, the delicate and compact nature of
the NPC, and fast and high throughput of bidirectional traffic in it have challenged the
investigation of these disordered domains. Computational and theoretical modeling approaches
offer a useful alternative towards understanding the disordered FG-repeat domains in the NPC
[2,3].
Objective: We aim to explore the conformational behavior of the disordered FG-repeat domains
in the NPC central channel.
Methods: 3D coarse-grained models of the yeast central channel are develped with all 11 known
FG nucleoporins (Nups). The exact sequence of the FG Nups disordered domains are extracted
and their length, hydrophobicity, charge, and the native grafting density are incorporated in the
model.
Results: Our results show that the FG-motifs of these disordered domains are mainly
concentrated towards the central part of the channel, while charged residues are predominantly
localized near the central channel wall. Depending on the nuclear pore diameter, FG-repeats can
either make a channel-filling hydrogel or a thick lubricating layer, consistent with two differing
models proposed in the literature.
References:
[1] Jamali et al. (2011) Nuclear Pore Complex: Biochemistry and Biophysics of
Nucleocytoplasmic Transport in Health and Disease. International Review of Cell and Molecular
Biology. 287: 233-286.
[2] Moussavi-Baygi et al. (2011) Biophysical Coarse-Grained Modeling Provides Insights into
Transport through the Nuclear Pore Complex. Biophysical Journal. 100(6):1410-1419.
[3] Azimi et al. (2013) Higher Nucleoporin-Importinβ Affinity at the Nuclear Basket Increases
Nucleocytoplasmic Import. PLoS One. 8(11):e81741.
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