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PLoS One. 2017 Jan 20;12(1):e0170530. doi: 10.1371/journal.pone.0170530. eCollection 2017.

Peptide Targeted by Human Antibodies Associated with HIV Vaccine-Associated Protection Assumes a Dynamic α-Helical Structure.

Author information

1
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, United States of America.
2
The New York Structural Biology Center, New York, New York, United States of America.
3
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
4
Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
5
Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America.

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.

PMID:
28107435
PMCID:
PMC5249078
DOI:
10.1371/journal.pone.0170530
[Indexed for MEDLINE]
Free PMC Article

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