Cargo surface hydrophobicity is sufficient to overcome the nuclear pore complex selectivity barrier.
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.
Naim
Bracha
B
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Zbaida
David
D
Dagan
Shlomi
S
Kapon
Ruti
R
Reich
Ziv
Z
D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002467:Cell Nucleus / Q000378:metabolism; D016000:Cluster Analysis; D005998:Glycine / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D022022:Nuclear Pore / Q000378:metabolism*; D010539:Permeability; D010649:Phenylalanine / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013499:Surface Properties
D012710:Serum Albumin, Bovine; D010649:Phenylalanine; D005998:Glycine
J Biol Chem. 2007 Oct 26;282(43):31437-43
17726020
Trends Cell Biol. 2003 Dec;13(12):622-8
14624840
J Biol Chem. 2003 Oct 24;278(43):42699-709
12917401
Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16101-6
18845677
J Struct Biol. 2007 Aug;159(2):277-89
17446086
Traffic. 2005 May;6(5):421-7
15813752
Int Rev Cell Mol Biol. 2008;267:299-342
18544502
Annu Rev Biochem. 1998;67:265-306
9759490
J Biol Chem. 2007 Sep 28;282(39):28759-28767
17656361
J Cell Biol. 2003 Aug 4;162(3):391-401
12885761
PLoS Comput Biol. 2007 Jul;3(7):e125
17630825
Cell. 2007 Aug 10;130(3):405-7
17693250
Microbiol Mol Biol Rev. 2001 Dec;65(4):570-94, table of contents
11729264
Cell. 2003 Feb 21;112(4):441-51
12600309
Mol Biol Cell. 1997 Jun;8(6):945-56
9201707
J Mol Biol. 1999 Oct 29;293(3):579-93
10543952
J Mol Biol. 2007 Feb 9;366(1):330-45
17161424
EMBO J. 1997 Mar 17;16(6):1153-63
9135132
Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9512-7
16769882
Science. 2006 Nov 3;314(5800):766-7
17082440
Cell. 1995 Apr 21;81(2):215-22
7736573
Biophys J. 2005 Mar;88(3):L17-9
15626697
Trends Biochem Sci. 2004 Apr;29(4):175-82
15082311
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2450-5
12604785
J Mol Biol. 2003 Oct 24;333(3):587-603
14556747
Structure. 2005 Dec;13(12):1869-79
16338415
Traffic. 2005 Mar;6(3):187-98
15702987
Dev Cell. 2003 Jun;4(6):775-89
12791264
Biophys J. 1999 Jul;77(1):217-28
10388751
Biochim Biophys Acta. 1969 Dec 30;192(3):528-30
5392314
Cell. 2007 Apr 6;129(1):83-96
17418788
Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11446-51
16861303
J Cell Biol. 2001 Jan 22;152(2):411-7
11266456
Structure. 2007 Aug;15(8):977-91
17698002
J Biol Chem. 2001 Oct 19;276(42):38820-9
11489893
Science. 2006 Nov 3;314(5800):766-7
17082441
EMBO J. 2001 Mar 15;20(6):1320-30
11250898
J Cell Biol. 2004 Nov 22;167(4):583-90
15557115
J Mol Biol. 2005 Jun 10;349(3):515-25
15878174
Science. 2007 Oct 26;318(5850):640-3
17916694
Genes Cells. 2000 Oct;5(10):777-87
11029654
Science. 2006 Nov 3;314(5800):815-7
17082456
J Cell Biol. 1997 Nov 17;139(4):841-9
9362503
Annu Rev Cell Dev Biol. 1999;15:607-60
10611974
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3185-90
11248053
Nat Cell Biol. 2004 Mar;6(3):197-206
15039779
Mol Cell Proteomics. 2008 Jan;7(1):121-31
17897934
J Cell Biol. 2000 Feb 21;148(4):635-51
10684247
Biophys J. 2009 Feb 18;96(4):1235-48
19217844
Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12743-8
17646647
Cell. 2006 Jun 16;125(6):1041-53
16777596
J Biol Chem. 2002 Dec 27;277(52):50597-606
12372823
Cell. 2007 Aug 10;130(3):512-23
17693259
Cell Mol Life Sci. 2003 Aug;60(8):1659-88
14504656
J Chem Phys. 2007 Sep 21;127(11):115101
17887882
J Cell Biol. 1990 Sep;111(3):807-16
2391365
Microbiol Mol Biol Rev. 1997 Jun;61(2):193-211
9184010
Nature. 2009 Feb 19;457(7232):1023-7
19098896
Biophys J. 2003 Nov;85(5):2977-87
14581200
Nat Rev Mol Cell Biol. 2007 Mar;8(3):195-208
17287812
J Biol Chem. 2007 Feb 9;282(6):3881-8
17164246
Nature. 1975 Mar 13;254(5496):109-14
1117994
EMBO J. 2002 Jun 3;21(11):2664-71
12032079
Cell. 2000 Jul 7;102(1):99-108
10929717
Trends Cell Biol. 1994 Oct;4(10):357-65
14731624