title: Nuclear pore complex protein sequences determine overall copolymer brush structure and function.
abstract: The transport of cargo across the nuclear membrane is highly selective and accomplished by a poorly understood mechanism involving hundreds of nucleoporins lining the inside of the nuclear pore complex (NPC). Currently, there is no clear picture of the overall structure formed by this collection of proteins within the pore, primarily due to their disordered nature. We perform coarse-grained simulations of both individual nucleoporins and grafted rings of nups mimicking the in vivo geometry of the NPC and supplement this with polymer brush modeling. Our results indicate that different regions or blocks of an individual NPC protein can have distinctly different forms of disorder and that this property appears to be a conserved functional feature. Furthermore, this block structure at the individual protein level is critical to the formation of a unique higher-order polymer brush architecture that can exist in distinct morphologies depending on the effective interaction energy between the phenylalanine glycine (FG) domains of different nups. Because the interactions between FG domains may be modulated by certain forms of transport factors, our results indicate that transitions between brush morphologies could play an important role in regulating transport across the NPC, suggesting novel forms of gated transport across membrane pores with wide biomimetic applicability.
authors.affiliation: Department of Physics, University of California at Merced, Merced, California.
authors.forename: David
authors.initials: D
authors.lastname: Ando
authors.affiliation: Department of Physics, University of California at Riverside, Riverside, California.
authors.forename: Roya
authors.initials: R
authors.lastname: Zandi
authors.affiliation: Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Yong Woon
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Chemical Biology, University of California at Merced, Merced, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Colvin
authors.affiliation: Department of Molecular, Cell, and Developmental Biology, University of California at Santa Cruz, Santa Cruz, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Rexach
authors.affiliation: Department of Physics, University of California at Merced, Merced, California. Electronic address: agopinathan@ucmerced.edu.
authors.forename: Ajay
authors.initials: A
authors.lastname: Gopinathan
mesh_terms: D001692:Biological Transport; D019295:Computational Biology; D008958:Models, Molecular; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000378:metabolism*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid
chemical_list: D028861:Nuclear Pore Complex Proteins