title: Identification of the HIV-1 gp41 core-binding motif in the scaffolding domain of caveolin-1.
abstract: The human immunodeficiency virus, type 1 (HIV-1) gp41 core plays an important role in fusion between viral and target cell membranes. A single chain polypeptide, N36(L8)C34, which forms a six-helix bundle in physiological solution, can be used as a model of gp41 core. Here we identified from a 12-mer phage peptide library a positive phage clone displaying a peptide sequence with high binding activity to the HIV-1 gp41 core. The peptide sequence contains a putative gp41-binding motif, PhiXXXXPhiXPhi (X is any amino acid residue, and Phi is any one of the aromatic amino acid residues Trp, Phe, or Tyr). This motif also exists in the scaffolding domain of caveolin-1 (Cav-1), a known gp41-binding protein. Cav-1-(61-101) and Cav-1-(82-101), two recombinant fusion proteins containing the Cav-1 scaffolding domain, bound significantly to the gp41 expressed in mammalian cells and interacted with the polypeptide N36(L8)C34. These results suggest that the scaffolding domain of Cav-1 may bind to the gp41 core via the motif. This interaction may be essential for formation of fusion pore or endocytosis of HIV-1 and affect the pathogenesis of HIV-1 infection. Further characterization of the gp41 core-binding motifs may shed light on the alternative mechanism by which HIV-1 enters into the target cell.
authors.affiliation: Laboratory of Immunology, Department of Biology, Tsinghua University, Protein Science Laboratory of the Ministry of Education, Beijing 100084, P.R. China.
authors.forename: Jing-He
authors.initials: JH
authors.lastname: Huang
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Chen
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D051242:Caveolin 1 / Q000737:chemistry* / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D010446:Peptide Fragments; D019151:Peptide Library; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins
chemical_list: D051242:Caveolin 1; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D019151:Peptide Library; D011993:Recombinant Fusion Proteins