A Physical Model Describing the Interaction of Nuclear Transport Receptors with FG Nucleoporin Domain Assemblies

Overview

Journal Elife

Specialty Biology

Date 2016 Apr 9

PMID 27058170

Citations 43

Authors

Raphael Zahn

Dino Osmanovic

Severin Ehret

Carolina Araya Callis

Steffen Frey

Murray Stewart

Changjiang You

Dirk Gorlich

Bart W Hoogenboom

Ralf P Richter

Affiliations

Soon will be listed here.

Abstract

The permeability barrier of nuclear pore complexes (NPCs) controls bulk nucleocytoplasmic exchange. It consists of nucleoporin domains rich in phenylalanine-glycine motifs (FG domains). As a bottom-up nanoscale model for the permeability barrier, we have used planar films produced with three different end-grafted FG domains, and quantitatively analyzed the binding of two different nuclear transport receptors (NTRs), NTF2 and Importin β, together with the concomitant film thickness changes. NTR binding caused only moderate changes in film thickness; the binding isotherms showed negative cooperativity and could all be mapped onto a single master curve. This universal NTR binding behavior - a key element for the transport selectivity of the NPC - was quantitatively reproduced by a physical model that treats FG domains as regular, flexible polymers, and NTRs as spherical colloids with a homogeneous surface, ignoring the detailed arrangement of interaction sites along FG domains and on the NTR surface.

Citing Articles

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References

Moussavi-Baygi R, Jamali Y, Karimi R, Mofrad M . Biophysical coarse-grained modeling provides insights into transport through the nuclear pore complex. Biophys J. 2011; 100(6):1410-9. PMC: 3059569. DOI: 10.1016/j.bpj.2011.01.061. View

Opferman M, Coalson R, Jasnow D, Zilman A . Morphological control of grafted polymer films via attraction to small nanoparticle inclusions. Phys Rev E Stat Nonlin Soft Matter Phys. 2012; 86(3 Pt 1):031806. DOI: 10.1103/PhysRevE.86.031806. View

Eibauer M, Pellanda M, Turgay Y, Dubrovsky A, Wild A, Medalia O . Structure and gating of the nuclear pore complex. Nat Commun. 2015; 6:7532. PMC: 4491817. DOI: 10.1038/ncomms8532. View

Rout M, Wente S . Pores for thought: nuclear pore complex proteins. Trends Cell Biol. 1994; 4(10):357-65. DOI: 10.1016/0962-8924(94)90085-x. View

Grossman E, Medalia O, Zwerger M . Functional architecture of the nuclear pore complex. Annu Rev Biophys. 2012; 41:557-84. DOI: 10.1146/annurev-biophys-050511-102328. View

Ando D, Zandi R, Kim Y, Colvin M, Rexach M, Gopinathan A . Nuclear pore complex protein sequences determine overall copolymer brush structure and function. Biophys J. 2014; 106(9):1997-2007. PMC: 4017316. DOI: 10.1016/j.bpj.2014.03.021. View

Denning D, Uversky V, Patel S, Fink A, Rexach M . The Saccharomyces cerevisiae nucleoporin Nup2p is a natively unfolded protein. J Biol Chem. 2002; 277(36):33447-55. DOI: 10.1074/jbc.M203499200. View

Macara I . Transport into and out of the nucleus. Microbiol Mol Biol Rev. 2001; 65(4):570-94, table of contents. PMC: 99041. DOI: 10.1128/MMBR.65.4.570-594.2001. View

Eisele N, Andersson F, Frey S, Richter R . Viscoelasticity of thin biomolecular films: a case study on nucleoporin phenylalanine-glycine repeats grafted to a histidine-tag capturing QCM-D sensor. Biomacromolecules. 2012; 13(8):2322-32. DOI: 10.1021/bm300577s. View

10.

Bestembayeva A, Kramer A, Labokha A, Osmanovic D, Liashkovich I, Orlova E . Nanoscale stiffness topography reveals structure and mechanics of the transport barrier in intact nuclear pore complexes. Nat Nanotechnol. 2014; 10(1):60-64. PMC: 4286247. DOI: 10.1038/nnano.2014.262. View

11.

Fernandez-Martinez J, Rout M . A jumbo problem: mapping the structure and functions of the nuclear pore complex. Curr Opin Cell Biol. 2012; 24(1):92-9. PMC: 3472030. DOI: 10.1016/j.ceb.2011.12.013. View

12.

Ribbeck K, Gorlich D . Kinetic analysis of translocation through nuclear pore complexes. EMBO J. 2001; 20(6):1320-30. PMC: 145537. DOI: 10.1093/emboj/20.6.1320. View

13.

Clarkson W, Corbett A, Paschal B, Kent H, McCoy A, Gerace L . Nuclear protein import is decreased by engineered mutants of nuclear transport factor 2 (NTF2) that do not bind GDP-Ran. J Mol Biol. 1997; 272(5):716-30. DOI: 10.1006/jmbi.1997.1255. View

14.

Carton I, Brisson A, Richter R . Label-free detection of clustering of membrane-bound proteins. Anal Chem. 2010; 82(22):9275-81. DOI: 10.1021/ac102495q. View

15.

Floch A, Palancade B, Doye V . Fifty years of nuclear pores and nucleocytoplasmic transport studies: multiple tools revealing complex rules. Methods Cell Biol. 2014; 122:1-40. DOI: 10.1016/B978-0-12-417160-2.00001-1. View

16.

Gorlich D, Kutay U . Transport between the cell nucleus and the cytoplasm. Annu Rev Cell Dev Biol. 1999; 15:607-60. DOI: 10.1146/annurev.cellbio.15.1.607. View

17.

Peleg O, Tagliazucchi M, Kroger M, Rabin Y, Szleifer I . Morphology control of hairy nanopores. ACS Nano. 2011; 5(6):4737-47. DOI: 10.1021/nn200702u. View

18.

Keminer O, Peters R . Permeability of single nuclear pores. Biophys J. 1999; 77(1):217-28. PMC: 1300323. DOI: 10.1016/S0006-3495(99)76883-9. View

19.

Denning D, Patel S, Uversky V, Fink A, Rexach M . Disorder in the nuclear pore complex: the FG repeat regions of nucleoporins are natively unfolded. Proc Natl Acad Sci U S A. 2003; 100(5):2450-5. PMC: 151361. DOI: 10.1073/pnas.0437902100. View

20.

Bayliss R, Leung S, Baker R, Quimby B, Corbett A, Stewart M . Structural basis for the interaction between NTF2 and nucleoporin FxFG repeats. EMBO J. 2002; 21(12):2843-53. PMC: 126060. DOI: 10.1093/emboj/cdf305. View