Hydrophobicity as a possible reason for gelation of FG-rich nucleoporins.

In this work we address the question of whether hydrophobic parts of FG-rich nucleoporins can be the reason for their ability to form a hydro-gel (Frey et al. in Science 314:3, 2006). We focus on the N-terminal fsFG domain of the essential yeast nucleoporin Nsp1p (Hurt in EMBO J 7:4323, 1988) as a nucleoporin model system and on the question of whether a phase transition between a sol and a gel phase exists. The N-terminal fsFG domain comprises 18 regular FSFG repeats and 16 less regular FG repeats. This domain is modeled, and a Metropolis Monte-Carlo algorithm is used to generate equilibrated ensembles of peptide networks, which were then analyzed by percolation theoretical methods. We take into account the excluded volume of the protein backbone and all side chains that are at least medium-sized (starting with Glu/E) as well as the hydrophobic clusters of the amino acid sequence. There is a competition between two kinds of entropic forces in the system: the excluded volume interactions and the hydrophobic parts of the nucleoporin strands. Therefore, it is not a priori clear whether the system percolates at a biologically realistic density. Nevertheless, we find a sol-gel phase transition in the system at a critical density of 42 mg mL(-1). This may be considered a hint that hydrophobic nucleoporin parts are key for the formation of gels in the nuclear pore complex.