PT  - JOURNAL ARTICLE
AU  - Wesley G. Chen
AU  - Jacob Witten
AU  - Scott C. Grindy
AU  - Niels Holten-Andersen
AU  - Katharina Ribbeck
TI  - Charge influences substrate recognition and self-assembly of hydrophobic FG sequences
AID  - 10.1101/090159
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 090159
4099  - http://biorxiv.org/content/early/2016/12/12/090159.short
4100  - http://biorxiv.org/content/early/2016/12/12/090159.full
AB  - The nuclear pore complex controls the passage of molecules via hydrophobic phenylalanine-glycine (FG) domains on nucleoporins. Such FG-domains consist of repeating units of FxFG, FG, or GLFG sequences, which can be interspersed with highly charged amino acid sequences. Despite the high density of charge exhibited in certain FG-domains, if and how charge influences FG-domain self-assembly and selective binding of nuclear transport receptors is largely unexplored. Studying how individual charged amino acids contribute to nuclear pore selectivity is challenging with modern in vivo and in vitro techniques due to the complexity of nucleoporin sequences. Here, we present a rationally designed approach to deconstruct essential components of nucleoporins down to 14 amino acid sequences. With these nucleoporin-based peptides, we systematically dissect how charge type and placement of charge influences self-assembly and selective binding of FG-containing gels. Specifically, we find that charge type determines which hydrophobic substrates FG sequences recognize while spatial localization of charge tunes hydrophobic self-assembly and receptor selectivity of FG sequences.