Cargo Surface Hydrophobicity is Sufficient to Overcome the Nuclear Pore Complex Selectivity Barrier

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2009 Aug 15

PMID 19680225

Citations 38

Authors

Bracha Naim

David Zbaida

Shlomi Dagan

Ruti Kapon

Ziv Reich

Affiliations

Soon will be listed here.

Abstract

To fulfil their function, nuclear pore complexes (NPCs) must discriminate between inert proteins and nuclear transport receptors (NTRs), admitting only the latter. This specific permeation is thought to depend on interactions between hydrophobic patches on NTRs and phenylalanine-glycine (FG) or related repeats that line the NPC. Here, we tested this premise directly by conjugating different hydrophobic amino-acid analogues to the surface of an inert protein and examining its ability to cross NPCs unassisted by NTRs. Conjugation of as few as four hydrophobic moieties was sufficient to enable passage of the protein through NPCs. Transport of the modified protein proceeded with rates comparable to those measured for the innate protein when bound to an NTR and was relatively insensitive both to the nature and density of the amino acids used to confer hydrophobicity. The latter observation suggests a non-specific, small, and plant interaction network between cargo and FG repeats.

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References

Kramer A, Ludwig Y, Shahin V, Oberleithner H . A pathway separate from the central channel through the nuclear pore complex for inorganic ions and small macromolecules. J Biol Chem. 2007; 282(43):31437-43. DOI: 10.1074/jbc.M703720200. View

Rout M, Aitchison J, Magnasco M, Chait B . Virtual gating and nuclear transport: the hole picture. Trends Cell Biol. 2003; 13(12):622-8. DOI: 10.1016/j.tcb.2003.10.007. View

Pyhtila B, Rexach M . A gradient of affinity for the karyopherin Kap95p along the yeast nuclear pore complex. J Biol Chem. 2003; 278(43):42699-709. DOI: 10.1074/jbc.M307135200. View

Otsuka S, Iwasaka S, Yoneda Y, Takeyasu K, Yoshimura S . Individual binding pockets of importin-beta for FG-nucleoporins have different binding properties and different sensitivities to RanGTP. Proc Natl Acad Sci U S A. 2008; 105(42):16101-6. PMC: 2570979. DOI: 10.1073/pnas.0802647105. View

Lim R, Koser J, Huang N, Schwarz-Herion K, Aebi U . Nanomechanical interactions of phenylalanine-glycine nucleoporins studied by single molecule force-volume spectroscopy. J Struct Biol. 2007; 159(2):277-89. DOI: 10.1016/j.jsb.2007.01.018. View

Peters R . Translocation through the nuclear pore complex: selectivity and speed by reduction-of-dimensionality. Traffic. 2005; 6(5):421-7. DOI: 10.1111/j.1600-0854.2005.00287.x. View

Lim R, Ullman K, Fahrenkrog B . Biology and biophysics of the nuclear pore complex and its components. Int Rev Cell Mol Biol. 2008; 267:299-342. PMC: 4366138. DOI: 10.1016/S1937-6448(08)00632-1. View

Mattaj I, Englmeier L . Nucleocytoplasmic transport: the soluble phase. Annu Rev Biochem. 1998; 67:265-306. DOI: 10.1146/annurev.biochem.67.1.265. View

Yazicioglu M, Goad D, Ranganathan A, Whitehurst A, Goldsmith E, Cobb M . Mutations in ERK2 binding sites affect nuclear entry. J Biol Chem. 2007; 282(39):28759-28767. DOI: 10.1074/jbc.M703460200. View

10.

Bednenko J, Cingolani G, Gerace L . Importin beta contains a COOH-terminal nucleoporin binding region important for nuclear transport. J Cell Biol. 2003; 162(3):391-401. PMC: 2172684. DOI: 10.1083/jcb.200303085. View

11.

Zilman A, Di Talia S, Chait B, Rout M, Magnasco M . Efficiency, selectivity, and robustness of nucleocytoplasmic transport. PLoS Comput Biol. 2007; 3(7):e125. PMC: 1914370. DOI: 10.1371/journal.pcbi.0030125. View

12.

Weis K . The nuclear pore complex: oily spaghetti or gummy bear?. Cell. 2007; 130(3):405-7. DOI: 10.1016/j.cell.2007.07.029. View

13.

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

14.

Weis K . Regulating access to the genome: nucleocytoplasmic transport throughout the cell cycle. Cell. 2003; 112(4):441-51. DOI: 10.1016/s0092-8674(03)00082-5. View

15.

Chi N, Adam S . Functional domains in nuclear import factor p97 for binding the nuclear localization sequence receptor and the nuclear pore. Mol Biol Cell. 1997; 8(6):945-56. PMC: 305705. DOI: 10.1091/mbc.8.6.945. View

16.

Bayliss R, Ribbeck K, Akin D, Kent H, Feldherr C, Gorlich D . Interaction between NTF2 and xFxFG-containing nucleoporins is required to mediate nuclear import of RanGDP. J Mol Biol. 1999; 293(3):579-93. DOI: 10.1006/jmbi.1999.3166. View

17.

Isgro T, Schulten K . Association of nuclear pore FG-repeat domains to NTF2 import and export complexes. J Mol Biol. 2006; 366(1):330-45. DOI: 10.1016/j.jmb.2006.11.048. View

18.

Kutay U, Izaurralde E, Bischoff F, Mattaj I, Gorlich D . Dominant-negative mutants of importin-beta block multiple pathways of import and export through the nuclear pore complex. EMBO J. 1997; 16(6):1153-63. PMC: 1169714. DOI: 10.1093/emboj/16.6.1153. View

19.

Lim R, Huang N, Koser J, Deng J, Lau K, Schwarz-Herion K . Flexible phenylalanine-glycine nucleoporins as entropic barriers to nucleocytoplasmic transport. Proc Natl Acad Sci U S A. 2006; 103(25):9512-7. PMC: 1480438. DOI: 10.1073/pnas.0603521103. View

20.

Burke B . Cell biology. Nuclear pore complex models gel. Science. 2006; 314(5800):766-7. DOI: 10.1126/science.1135739. View