Structural comparison of a 15 residue peptide from the V3 loop of HIV-1IIIb and an O-glycosylated analogue.

Abstract

As part of a program to study the effect of glycosylation on the three-dimensional structures of HIV-1IIIB V3 peptide constructs, we have examined the solution structures of a 15 residue peptide (RIQRGPGRAFVTIGK, P18IIIB)- originally mapped as an epitope recognized by CD8+ Dd class I MHC-restricted murine cytotoxic T-lymphocytes (CTL), and an analogue (P18IIIB-g), O-glycosylated with an alpha-galactosamine on Thr-12, using NMR, circular dichroism and molecular modeling methods. Our studies show that the peptides sample mainly random conformations in aqueous solution near 25 degrees C and become more ordered by the addition of trifluoroethanol. Upon decreasing the temperature to 5 degrees C, a reverse turn is formed around the immunodominant tip (G5-R8). Glycosylation on T12 'tightens' the turn slightly as suggested by NOE and CD analysis. In addition, the sugar has a defined conformation with respect to the peptide backbone and influences the local peptide conformation. These data suggest that simple glycosylation may influence the conformational equilibrium of a V3 peptide which contains a domain critical for antibody recognition and virus neutralization. We also show that the ability of cytotoxic T-lymphocytes (CTL) to lyse tumor cells presenting P18IIIB was completely abrogated by threonine glycosylation.

• Authors: X Huang, M C Smith, J A Berzofsky, J J Barchi Jr
• Journal: FEBS letters (FEBS Lett) Vol. 393 Issue 2-3 Pg. 280-6 (Sep 16 1996) ISSN: 0014-5793 [Print] England
• PMID: 8814305 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Glycopeptides
• HIV Envelope Protein gp120
• Peptide Fragments
• Threonine
• Galactosamine

Topics

• Amino Acid Sequence
• Animals
• Circular Dichroism
• Galactosamine
• Glycopeptides (chemistry)
• Glycosylation
• HIV Envelope Protein gp120 (chemistry, immunology)
• HIV-1 (chemistry, immunology)
• Humans
• Magnetic Resonance Spectroscopy
• Mice
• Models, Molecular
• Molecular Sequence Data
• Molecular Structure
• Peptide Fragments (chemistry)
• Protein Conformation
• Spectrometry, Mass, Fast Atom Bombardment
• T-Lymphocytes, Cytotoxic (immunology)
• Threonine