title: Nucleoporin's Like Charge Regions Are Major Regulators of FG Coverage and Dynamics Inside the Nuclear Pore Complex.
abstract: Nucleocytoplasmic transport has been the subject of a large body of research in the past few decades. Recently, the focus of investigations in this field has shifted from studies of the overall function of the nuclear pore complex (NPC) to the examination of the role of different domains of phenylalanine-glycine nucleoporin (FG Nup) sequences on the NPC function. In our recent bioinformatics study, we showed that FG Nups have some evolutionarily conserved sequence-based features that might govern their physical behavior inside the NPC. We proposed the 'like charge regions' (LCRs), sequences of charged residues with only one type of charge, as one of the features that play a significant role in the formation of FG network inside the central channel. In this study, we further explore the role of LCRs in the distribution of FG Nups, using a recently developed coarse-grained molecular dynamics model. Our results demonstrate how LCRs affect the formation of two transport pathways. While some FG Nups locate their FG network at the center of the NPC forming a homogeneous meshwork of FG repeats, other FG Nups cover the space adjacent to the NPC wall. LCRs in the former group, i.e. FG Nups that form an FG domain at the center, tend to regulate the size of the highly dense, doughnut-shaped FG meshwork and leave a small low FG density area at the center of the pore for passive diffusion. On the other hand, LCRs in the latter group of FG Nups enable them to maximize their interactions and cover a larger space inside the NPC to increase its capability to transport numerous cargos at the same time. Finally, a new viewpoint is proposed that reconciles different models for the nuclear pore selective barrier function.
authors.affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, California, United States of America.
authors.forename: Mohaddeseh
authors.initials: M
authors.lastname: Peyro
authors.affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, California, United States of America.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Soheilypour
authors.affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, California, United States of America.
authors.forename: Ali
authors.initials: A
authors.lastname: Ghavami
authors.affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, California, United States of America.
authors.forename: Mohammad R K
authors.initials: MR
authors.lastname: Mofrad
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing; D019943:Amino Acid Substitution; D019295:Computational Biology; D005998:Glycine / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009154:Mutation; D022022:Nuclear Pore / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C062748:NSP1 protein, S cerevisiae; C109212:NUP42 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C118587:SH2D3A protein, human; D029701:Saccharomyces cerevisiae Proteins; D010649:Phenylalanine; D005998:Glycine