Disordered Motifs and Domains in Cell Control - October 11-15, 2014

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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