title: Inter-subunit disulfide bonds in soluble HIV-1 envelope glycoprotein trimers.
abstract: Soluble forms of the trimeric human immunodeficiency virus (HIV-1) envelope glycoproteins are important tools for structural studies and in the construction of improved immunogens. We found that a substantial fraction of soluble envelope glycoprotein trimers contain inter-subunit disulfide bonds (inter-S-S bonds) that render the trimers resistant to heat and denaturing agents. These inter-S-S bonds can be reduced without disrupting the trimers by treatment with a low concentration of beta-mercaptoethanol or DTT. Antibody mapping studies suggest that the soluble HIV-1 envelope glycoprotein trimers lacking the inter-S-S bonds exhibit a conformation closer to that of the native HIV-1 envelope glycoprotein complex. However, reducing these inter-S-S bonds had only modest effects on the inefficient elicitation of neutralizing antibodies by the soluble trimers. These studies provide guidance in improving the resemblance of tractable, soluble forms of the HIV-1 envelope glycoproteins to the native virion spikes.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
authors.forename: Stewart
authors.initials: S
authors.lastname: Craig
authors.forename: Xinzhen
authors.initials: X
authors.lastname: Yang
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D000818:Animals; D002460:Cell Line; D004220:Disulfides / Q000737:chemistry*; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D051379:Mice
chemical_list: D004220:Disulfides; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41