title: Oligomer-specific conformations of the human immunodeficiency virus (HIV-1) gp41 envelope glycoprotein ectodomain recognized by human monoclonal antibodies.
abstract: Trimerization of the human immunodeficiency virus (HIV-1) envelope glycoproteins is mediated by the ectodomain of the gp41 transmembrane glycoprotein. Here we investigate oligomer-specific conformations of gp41 by using monoclonal antibodies (MAbs) from HIV-1-infected humans. Human MAbs directed against the cluster I region of gp41 recognized trimeric, dimeric, and monomeric forms of soluble envelope glycoproteins; thus, the integrity of the cluster I epitopes is minimally affected by the oligomeric state. In contrast, human MAbs to the cluster II region were all oligomers specific. One cluster II MAb, 126-6, recognized exclusively the trimeric form of envelope glycoproteins, whereas the others recognized both trimeric and dimeric forms. Thus, a distinct trimer-specific conformation exists in the cluster II region of gp41. Analysis of soluble envelope glycoprotein mutants revealed that gp41 sequences immediately N-terminal to isoleucine 646 contribute to the formation of both the trimer and the trimer-specific conformational epitope.
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. wy5e@virginia.edu
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Marta
authors.initials: M
authors.lastname: Kasterka
authors.forename: Miroslaw K
authors.initials: MK
authors.lastname: Gorny
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization
chemical_list: D000911:Antibodies, Monoclonal; D018985:Epitopes, B-Lymphocyte; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; C514787:gp41 protein, Human immunodeficiency virus 1