|Title||Charge Influences Substrate Recognition and Self-Assembly of Hydrophobic|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Chen, WG, Witten, J, Grindy, SC, Holten-Andersen, N, Ribbeck, K|
|Pagination||2088 - 2099|
|Keywords||hydrogel, molecular-mechanism, nuclear-pore complex, nucleoporins, permeability barrier, protein import, saccharomyces-cerevisiae, spider silk, translocation, transport|
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, many of which are interspersed with highly charged amino acid sequences. Despite the high density of charge in certain FG domains, if and how charge influences FG-domain self-assembly and selective binding of nuclear transport receptors is largely unexplored. Using rationally designed short peptide sequences, we determined that the charge type and identity of amino acids surrounding FG sequences impact the structure and selectivity of FG-based gels. Moreover, we showed that spatial localization of the charged amino acids with respect to the FG sequence determines the degree to which charge influences hydrophobic interactions. Taken together, our study highlights that charge type and placement of amino acids regulate FG-sequence function and are important considerations when studying the mechanism of nuclear pore complex transport in vivo.
|Short Title||Biophys. J.|