Conformational characterization of aberrant disulfide-linked HIV-1 gp120 dimers secreted from overexpressing cells.
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.
Finzi
Andrés
A
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Pacheco
Beatriz
B
Zeng
Xin
X
Kwon
Young Do
YD
Kwong
Peter D
PD
Sodroski
Joseph
J
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
D004220:Disulfides; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1
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