title: Peptide Targeted by Human Antibodies Associated with HIV Vaccine-Associated Protection Assumes a Dynamic α-Helical Structure.
abstract: The only evidence of vaccine-induced protection from HIV acquisition in humans was obtained in the RV144 HIV vaccine clinical trial. One immune correlate of risk in RV144 was observed to be higher titers of vaccine-induced antibodies (Abs) reacting with a 23-mer non-glycosylated peptide with the same amino acid sequence as a segment in the second variable (V2) loop of the MN strain of HIV. We used NMR to analyze the dynamic 3D structure of this peptide. Distance restraints between spatially proximate inter-residue protons were calculated from NOE cross peak intensities and used to constrain a thorough search of all possible conformations of the peptide. α-helical folding was strongly preferred by part of the peptide. A high-throughput structure prediction of this segment in all circulating HIV strains demonstrated that α-helical conformations are preferred by this segment almost universally across all subtypes. Notably, α-helical conformations of this segment of the V2 loop cluster cross-subtype-conserved amino acids on one face of the helix and the variable amino acid positions on the other in a semblance of an amphipathic α-helix. Accordingly, some Abs that protected against HIV in RV144 may have targeted a specific, conserved α-helical peptide epitope in the V2 loop of HIV's surface envelope glycoprotein.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Aiyegbo
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Shmelkov
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Dominguez
authors.affiliation: The New York Structural Biology Center, New York, New York, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Goger
authors.affiliation: The New York Structural Biology Center, New York, New York, United States of America.
authors.forename: Shibani
authors.initials: S
authors.lastname: Battacharya
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Allan C
authors.initials: AC
authors.lastname: deCamp
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.|Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
authors.affiliation: Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America.
authors.forename: Phillip W
authors.initials: PW
authors.lastname: Berman
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Timothy
authors.initials: T
authors.lastname: Cardozo
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000276:immunology; D017124:Conserved Sequence / Q000235:genetics; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D000072756:Protein Conformation, alpha-Helical; D017510:Protein Folding
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; C514793:gp120 protein, Human immunodeficiency virus 1