title: Effect of charge, hydrophobicity, and sequence of nucleoporins on the translocation of model particles through the nuclear pore complex.
abstract: The molecular structure of the yeast nuclear pore complex (NPC) and the translocation of model particles have been studied with a molecular theory that accounts for the geometry of the pore and the sequence and anchoring position of the unfolded domains of the nucleoporin proteins (the FG-Nups), which control selective transport through the pore. The theory explicitly models the electrostatic, hydrophobic, steric, conformational, and acid-base properties of the FG-Nups. The electrostatic potential within the pore, which arises from the specific charge distribution of the FG-Nups, is predicted to be negative close to pore walls and positive along the pore axis. The positive electrostatic potential facilitates the translocation of negatively charged particles, and the free energy barrier for translocation decreases for increasing particle hydrophobicity. These results agree with the experimental observation that transport receptors that form complexes with hydrophilic/neutral or positively charged proteins to transport them through the NPC are both hydrophobic and strongly negatively charged. The molecular theory shows that the effects of electrostatic and hydrophobic interactions on the translocating potential are cooperative and nonequivalent due to the interaction-dependent reorganization of the FG-Nups in the presence of the translocating particle. The combination of electrostatic and hydrophobic interactions can give rise to complex translocation potentials displaying a combination of wells and barriers, in contrast to the simple barrier potential observed for a hydrophilic/neutral translocating particle. This work demonstrates the importance of explicitly considering the amino acid sequence and hydrophobic, electrostatic, and steric interactions in understanding the translocation through the NPC.
authors: Department of Biomedical Engineering, and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208, USA.
authors: Mario
authors: M
authors: Tagliazucchi
authors: Orit
authors: O
authors: Peleg
authors: Martin
authors: M
authors: Kröger
authors: Yitzhak
authors: Y
authors: Rabin
authors: Igal
authors: I
authors: Szleifer
mesh_terms: D000595:Amino Acid Sequence; D057927:Hydrophobic and Hydrophilic Interactions; D008954:Models, Biological; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D055672:Static Electricity
chemical_list: D028861:Nuclear Pore Complex Proteins
references: J Mol Biol. 1999 Oct 29;293(3):579-93
references: 10543952
references: Trends Cell Biol. 2003 Dec;13(12):622-8
references: 14624840
references: Nature. 2007 Nov 29;450(7170):695-701
references: 18046406
references: Biophys J. 2010 Apr 21;98(8):1658-67
references: 20409487
references: Science. 2006 Nov 3;314(5800):766-7
references: 17082441
references: Science. 1996 Mar 15;271(5255):1513-8
references: 8599106
references: J Biol Chem. 2000 Feb 25;275(8):5874-9
references: 10681579
references: J Am Chem Soc. 2011 Feb 23;133(7):2192-7
references: 21280574
references: Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6281-5
references: 20304795
references: PLoS Comput Biol. 2007 Jul;3(7):e125
references: 17630825
references: Nat Cell Biol. 2001 Dec;3(12):E267-9
references: 11781578
references: Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16911-6
references: 23043112
references: Structure. 2009 Mar 11;17(3):449-59
references: 19278659
references: Proc Natl Acad Sci U S A. 2012 May 8;109(19):7326-31
references: 22529346
references: Eukaryot Cell. 2009 Dec;8(12):1814-27
references: 19801417
references: Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):E351-8
references: 21690354
references: Cell. 2007 Apr 6;129(1):83-96
references: 17418788
references: J Am Chem Soc. 2011 Nov 9;133(44):17753-63
references: 21942450
references: Bioessays. 2009 Apr;31(4):466-77
references: 19274657
references: EMBO J. 2001 Mar 15;20(6):1320-30
references: 11250898
references: Trends Cell Biol. 2010 Aug;20(8):461-9
references: 20627572
references: Curr Opin Cell Biol. 2012 Feb;24(1):92-9
references: 22321828
references: Science. 2007 Oct 26;318(5850):640-3
references: 17916694
references: Traffic. 2005 May;6(5):421-7
references: 15813752
references: PLoS Comput Biol. 2010 Apr 22;6(4):e1000747
references: 20421988
references: PLoS Comput Biol. 2011 Jun;7(6):e1002049
references: 21673865
references: Annu Rev Biochem. 2011;80:613-43
references: 21495847
references: J Cell Biol. 2000 Feb 21;148(4):635-51
references: 10684247
references: Biol Chem. 2010 Jul;391(7):719-30
references: 20482319
references: Traffic. 2003 Mar;4(3):127-35
references: 12656985
references: J Mol Biol. 2007 Jan 5;365(1):50-65
references: 17056062
references: Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12887-92
references: 15306682
references: EMBO J. 2002 Jun 17;21(12):2843-53
references: 12065398
references: ACS Nano. 2011 Jun 28;5(6):4737-47
references: 21524134
references: Biophys J. 2004 Apr;86(4):2008-16
references: 15041643
references: Nature. 2007 Nov 29;450(7170):683-94
references: 18046405
references: EMBO J. 2002 Jun 3;21(11):2664-71
references: 12032079
references: Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5300-5
references: 20203008
references: Nanotechnology. 2012 Aug 10;23(31):315101
references: 22796738
references: Cell. 2000 Jul 7;102(1):99-108
references: 10929717
references: Nature. 2010 Sep 30;467(7315):600-3
references: 20811366