Physical motif clustering within intrinsically disordered nucleoporin sequences reveals universal functional features.
Bioinformatics of disordered proteins is especially challenging given high mutation rates for homologous proteins and that functionality may not be strongly related to sequence. Here we have performed a novel bioinformatic analysis, based on the spatial clustering of physically relevant features such as binding motifs and charges within disordered proteins, on thousands of Nuclear Pore Complex (NPC) FG motif containing proteins (FG nups). The biophysical mechanism by which FG nups regulate nucleocytoplasmic transport has remained elusive. Our analysis revealed a set of highly conserved spatial features in the sequence structure of individual FG nups, such as the separation, localization, and ordering of FG motifs and charged residues along the protein chain. These functionally conserved features provide insight into the particular biophysical mechanisms responsible for regulation of nucleocytoplasmic traffic in the NPC, strongly constraining current models. Additionally this method allows us to identify potentially functionally analogous disordered proteins across distantly related species.
Physics Department, University of California Merced, Merced, California, United States of America.
David
D
Ando
Michael
M
Colvin
Michael
M
Rexach
Ajay
A
Gopinathan
D019295:Computational Biology; D006801:Humans; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics
C091559:NUP57 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human; D029701:Saccharomyces cerevisiae Proteins