title: GLUE that sticks to HIV: a helix-grafted GLUE protein that selectively binds the HIV gp41 N-terminal helical region.
abstract: Methods for the stabilization of well-defined helical peptide drugs and basic research tools have received considerable attention in the last decade. Here, we report the stable and functional display of an HIV gp41 C-peptide helix mimic on a GRAM-Like Ubiquitin-binding in EAP45 (GLUE) protein. C-peptide helix-grafted GLUE selectively binds a mimic of the N-terminal helical region of gp41, a well-established HIV drug target, in a complex cellular environment. Additionally, the helix-grafted GLUE is folded in solution, stable in human serum, and soluble in aqueous solutions, and thus overcomes challenges faced by a multitude of peptide drugs, including those derived from HIV gp41 C-peptide.
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523 (USA).
authors.forename: Susanne N
authors.initials: SN
authors.lastname: Walker
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Tennyson
authors.forename: Alex M
authors.initials: AM
authors.lastname: Chapman
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Kennan
authors.forename: Brian R
authors.initials: BR
authors.lastname: McNaughton
mesh_terms: D001665:Binding Sites; D002942:Circular Dichroism; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry* / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D018716:Molecular Mimicry; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D015700:HIV Envelope Protein gp41; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C516152:VPS36 protein, human; C491128:Vps36 protein, S cerevisiae; C514787:gp41 protein, Human immunodeficiency virus 1
keywords: HIV/AIDS; gp41; helix grafting; protein engineering; protein-protein interactions