title: HIV-1 capsid undergoes coupled binding and isomerization by the nuclear pore protein NUP358.
abstract: BACKGROUND
  Lentiviruses such as HIV-1 can be distinguished from other retroviruses by the cyclophilin A-binding loop in their capsid and their ability to infect non-dividing cells. Infection of non-dividing cells requires transport through the nuclear pore but how this is mediated is unknown.
  
  
  RESULTS
  Here we present the crystal structure of the N-terminal capsid domain of HIV-1 in complex with the cyclophilin domain of nuclear pore protein NUP358. The structure reveals that HIV-1 is positioned to allow single-bond resonance stabilisation of exposed capsid residue P90. NMR exchange experiments demonstrate that NUP358 is an active isomerase, which efficiently catalyzes cis-trans isomerization of the HIV-1 capsid. In contrast, the distantly related feline lentivirus FIV can bind NUP358 but is neither isomerized by it nor requires it for infection.
  
  
  CONCLUSIONS
  Isomerization by NUP358 may be preserved by HIV-1 to target the nuclear pore and synchronize nuclear entry with capsid uncoating.
authors.affiliation: Protein and Nucleic Acid Chemistry Division, Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
authors.forename: Katsiaryna
authors.initials: K
authors.lastname: Bichel
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Price
authors.forename: Torsten
authors.initials: T
authors.lastname: Schaller
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Towers
authors.forename: Stefan M V
authors.initials: SM
authors.lastname: Freund
authors.forename: Leo C
authors.initials: LC
authors.lastname: James
mesh_terms: D002213:Capsid / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D015497:HIV-1 / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D053586:Virus Internalization; D057646:Virus Uncoating
chemical_list: D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; C094493:ran-binding protein 2
references.citation: J Cell Sci. 1993 Sep;106 ( Pt 1):261-74
references.pmid: 8270630
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6200-5
references.pmid: 17400754
references.citation: Nat Struct Biol. 2003 Jun;10(6):475-81
references.pmid: 12730686
references.citation: Science. 2008 Feb 15;319(5865):921-6
references.pmid: 18187620
references.citation: Nature. 2005 Nov 3;438(7064):117-21
references.pmid: 16267559
references.citation: PLoS One. 2010 Dec 14;5(12):e15620
references.pmid: 21179483
references.citation: Mol Cell Biol. 2004 Mar;24(6):2373-84
references.pmid: 14993277
references.citation: Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1556-61
references.pmid: 9037092
references.citation: Virology. 2002 Mar 15;294(2):289-95
references.pmid: 12009870
references.citation: Cell. 1996 Dec 27;87(7):1285-94
references.pmid: 8980234
references.citation: Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3
references.pmid: 15299374
references.citation: Nat Chem Biol. 2010 May;6(5):331-7
references.pmid: 20364129
references.citation: Science. 1996 Jul 12;273(5272):231-5
references.pmid: 8662505
references.citation: Cell. 2003 Feb 21;112(4):441-51
references.pmid: 12600309
references.citation: Curr Opin Cell Biol. 2006 Jun;18(3):342-7
references.pmid: 16631361
references.citation: Nature. 1994 Nov 24;372(6504):359-62
references.pmid: 7969494
references.citation: Mol Biol Cell. 2012 Mar;23(6):1115-28
references.pmid: 22262462
references.citation: Philos Trans R Soc Lond B Biol Sci. 2009 Mar 12;364(1517):675-87
references.pmid: 19038776
references.citation: Cell. 1997 Jan 10;88(1):97-107
references.pmid: 9019411
references.citation: PLoS Pathog. 2009 May;5(5):e1000437
references.pmid: 19478882
references.citation: Cell Host Microbe. 2010 Mar 18;7(3):221-33
references.pmid: 20227665
references.citation: Proc Natl Acad Sci U S A. 2011 Jun 14;108(24):9975-80
references.pmid: 21628558
references.citation: Traffic. 2012 Feb;13(2):218-33
references.pmid: 21995724
references.citation: Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
references.pmid: 15299926
references.citation: Biochemistry. 2004 May 25;43(20):6110-9
references.pmid: 15147195
references.citation: J Virol. 2005 Jan;79(1):176-83
references.pmid: 15596813
references.citation: Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
references.pmid: 20057044
references.citation: J Virol. 2004 Jun;78(11):5670-8
references.pmid: 15140964
references.citation: Annu Rev Med. 2008;59:487-501
references.pmid: 17845138
references.citation: PLoS One. 2012;7(9):e46037
references.pmid: 23049930
references.citation: EMBO J. 2007 Jun 20;26(12):3025-37
references.pmid: 17557080
references.citation: J Biomol NMR. 1994 Sep;4(5):727-34
references.pmid: 7919956
references.citation: Nat Med. 2003 Sep;9(9):1138-43
references.pmid: 12897779
references.citation: Virology. 2006 Jan 5;344(1):88-93
references.pmid: 16364740
references.citation: J Virol. 2010 Jan;84(1):397-406
references.pmid: 19846519
references.citation: Curr Opin Virol. 2011 Oct;1(4):226-32
references.pmid: 22440781
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5247-52
references.pmid: 11929983
references.citation: Retrovirology. 2006 Oct 12;3:70
references.pmid: 17038183
references.citation: Nature. 1995 Jul 13;376(6536):184-8
references.pmid: 7603572
references.citation: Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
references.pmid: 20383002
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13324-8
references.pmid: 15326303
references.citation: PLoS Pathog. 2011 Mar;7(3):e1001313
references.pmid: 21423673
references.citation: Nat Struct Mol Biol. 2009 Oct;16(10):1036-42
references.pmid: 19767750
references.citation: EMBO J. 1993 May;12(5):2099-108
references.pmid: 8491198
references.citation: J Mol Biol. 1997 Jun 27;269(5):780-95
references.pmid: 9223641
references.citation: J Cell Biol. 2002 Jul 8;158(1):63-77
references.pmid: 12105182
references.citation: J Virol. 2007 Nov;81(21):11713-21
references.pmid: 17728224
references.citation: J Mol Biol. 2013 Apr 26;425(8):1318-29
references.pmid: 23353830
references.citation: J Virol. 1996 Jul;70(7):4220-7
references.pmid: 8676442
references.citation: Nature. 2004 Feb 26;427(6977):848-53
references.pmid: 14985764
references.citation: Nature. 2005 Jun 2;435(7042):687-92
references.pmid: 15931224
references.citation: PLoS Pathog. 2011 Dec;7(12):e1002439
references.pmid: 22174692
references.citation: Cell. 1993 Jun 18;73(6):1067-78
references.pmid: 8513493
references.citation: J Biol Chem. 1995 Jun 9;270(23):14209-13
references.pmid: 7775481
references.citation: Cell. 2008 Oct 3;135(1):49-60
references.pmid: 18854154
references.citation: J Virol. 1997 Mar;71(3):2107-13
references.pmid: 9032343
references.citation: J Virol. 2004 Dec;78(23):12800-8
references.pmid: 15542632
references.citation: EMBO J. 2001 Mar 15;20(6):1300-9
references.pmid: 11250896
references.citation: Structure. 1994 Jan 15;2(1):33-44
references.pmid: 8075981
references.citation: J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
references.pmid: 19461840
references.citation: J Mol Biol. 2010 Nov 12;403(5):723-38
references.pmid: 20708627
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3557-62
references.pmid: 18287035
references.citation: Curr Biol. 2008 Aug 26;18(16):1192-202
references.pmid: 18722123
references.citation: J Virol. 1996 Aug;70(8):5170-6
references.pmid: 8764025
references.citation: Nat Rev Microbiol. 2007 Mar;5(3):187-96
references.pmid: 17304248