title: Conformational characterization of aberrant disulfide-linked HIV-1 gp120 dimers secreted from overexpressing cells.
abstract: The envelope (Env) glycoproteins of human immunodeficiency virus (HIV-1) mediate viral entry and are also the primary target of neutralizing antibodies. The gp160 envelope glycoprotein precursor undergoes proteolytic cleavage in the Golgi complex to produce the gp120 exterior glycoprotein and the gp41 transmembrane glycoprotein, which remain associated non-covalently in the trimeric Env complex. Monomeric soluble gp120 has been used extensively to investigate conformational states, structure, antigenicity and immunogenicity of the HIV-1 Env glycoproteins. Expression of gp120 alone (without gp41) leads to the accumulation not only of monomeric gp120 but also an aberrant dimeric form. The gp120 dimers were sensitive to reducing agents. The formation of gp120 dimers was disrupted by a single amino acid change in the inner domain, and was reduced by removal of the V1/V2 variable loops or the N and C termini. Epitopes on the gp120 inner domain and the chemokine receptor-binding surface were altered or occluded by gp120 dimerization. Awareness of the existence and properties of gp120 dimers should assist interpretation of studies of this key viral protein.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Andrés
authors.initials: A
authors.lastname: Finzi
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pacheco
authors.forename: Xin
authors.initials: X
authors.lastname: Zeng
authors.forename: Young Do
authors.initials: YD
authors.lastname: Kwon
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D002460:Cell Line; D004220:Disulfides; D015699:HIV Envelope Protein gp120 / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D055503:Protein Multimerization
chemical_list: D004220:Disulfides; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1
references.citation: Nature. 1996 Nov 14;384(6605):184-7
references.pmid: 8906796
references.citation: J Virol. 1998 Sep;72(9):7620-5
references.pmid: 9696864
references.citation: Science. 1996 Jun 28;272(5270):1955-8
references.pmid: 8658171
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15812-7
references.pmid: 14668432
references.citation: Nature. 1996 Nov 14;384(6605):179-83
references.pmid: 8906795
references.citation: J Virol. 1994 Jan;68(1):469-84
references.pmid: 7504741
references.citation: Virology. 1993 Mar;193(1):510-4
references.pmid: 8438588
references.citation: Nature. 1984 Dec 20-1985 Jan 2;312(5996):763-7
references.pmid: 6096719
references.citation: Med Microbiol Immunol. 1991;180(4):183-92
references.pmid: 1784269
references.citation: Cell. 1996 Jun 28;85(7):1149-58
references.pmid: 8674120
references.citation: Science. 1985 May 31;228(4703):1091-4
references.pmid: 2986290
references.citation: Nature. 2002 Dec 12;420(6916):678-82
references.pmid: 12478295
references.citation: J Virol. 1991 Apr;65(4):2119-23
references.pmid: 2002555
references.citation: Proc Natl Acad Sci U S A. 1990 Jan;87(2):648-52
references.pmid: 2300552
references.citation: J Virol. 1991 Jul;65(7):3797-803
references.pmid: 2041094
references.citation: Virology. 1989 Sep;172(1):367-9
references.pmid: 2672564
references.citation: J Virol. 2002 Oct;76(19):9888-99
references.pmid: 12208966
references.citation: Cell. 1996 Jun 28;85(7):1135-48
references.pmid: 8674119
references.citation: Cell. 1997 Apr 18;89(2):263-73
references.pmid: 9108481
references.citation: Nat Struct Biol. 1995 Dec;2(12):1075-82
references.pmid: 8846219
references.citation: Science. 1985 May 3;228(4699):593-5
references.pmid: 2984774
references.citation: Adv Exp Med Biol. 1991;300:203-19; discussion 220-1
references.pmid: 1781345
references.citation: J Virol. 2009 May;83(9):4476-88
references.pmid: 19211747
references.citation: Nature. 1998 Jun 18;393(6686):648-59
references.pmid: 9641677
references.citation: Nature. 2007 Feb 15;445(7129):732-7
references.pmid: 17301785
references.citation: J Virol. 1996 Mar;70(3):1863-72
references.pmid: 8627711
references.citation: J Virol. 1994 Sep;68(9):5854-62
references.pmid: 7520095
references.citation: Virology. 1990 Dec;179(2):827-33
references.pmid: 2238472
references.citation: Science. 1996 May 10;272(5263):872-7
references.pmid: 8629022
references.citation: Nature. 1997 May 22;387(6631):426-30
references.pmid: 9163431
references.citation: Science. 1986 Jan 24;231(4736):382-5
references.pmid: 3001934
references.citation: Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9026-31
references.pmid: 10922058
references.citation: J Virol. 1991 Nov;65(11):6188-93
references.pmid: 1717717
references.citation: Nature. 1996 Jun 20;381(6584):661-6
references.pmid: 8649511
references.citation: J Virol. 2009 Sep;83(17):8364-78
references.pmid: 19535453
references.citation: AIDS Res Hum Retroviruses. 1997 Dec 10;13(18):1549-59
references.pmid: 9430247
references.citation: Structure. 2000 Dec 15;8(12):1329-39
references.pmid: 11188697
references.citation: J Virol. 2004 Dec;78(23):12975-86
references.pmid: 15542649
references.citation: Mol Cell. 2010 Mar 12;37(5):656-67
references.pmid: 20227370
references.citation: J Virol. 2000 May;74(10):4448-55
references.pmid: 10775580
references.citation: J Virol. 1995 Sep;69(9):5723-33
references.pmid: 7543586
references.citation: Nature. 1984 Dec 20-1985 Jan 2;312(5996):767-8
references.pmid: 6083454
references.citation: Nature. 1996 Jun 20;381(6584):667-73
references.pmid: 8649512