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Scientific article
English

Molecular modeling of hen egg lysozyme HEL[52-61] peptide binding to I-A(k) MHC class II molecule

Published inInternational immunology, vol. 10, no. 12, p. 1753-1764
Publication date1998
Abstract

A bound conformation of the antigenic decapeptide hen egg lysozyme HEL[52-61] associated to the mouse MHC class II (MHC II) I-A(k) was modeled by homology with the three-dimensional structure of hemagglutinin HA[306-318]-HLA-DR1 complex, HEL peptide Tyr53 could not be aligned with the HA peptide Tyr308 because this resulted in a buried Tyr53 side chain within the I-A(k) peptide-binding groove and this conflicted with this side chain being recognized by T cells. Therefore, Asp52 of HEL was fixed as the P1 anchor and aligned on Tyr308 of HA, After molecular dynamics, the modeled complex was stable even in the absence of any constraint. The peptide backbone adopted a polyproline II-like conformation with canonical hydrogen bonding between the peptide backbone and MHC II molecule, Asp52, Ile55, Gln57 and Ser60 were predicted to be deeply buried into P1, P4, P6 and is MHC II pockets, and Tyr53, Leu56, Asn59 and Arg61 as TCR contacting residues. The modeling of 15 complexes associating I-A(k) with peptides derived from HEL[52-61] by single amino acid substitution proved stable with conserved hydrogen bonds and side chain orientation compatible with their recognition by two T cell hybridomas, Moreover, comparison with the recently solved crystal structure of the related HEL[50-62]-I-A(k) complex revealed striking similarities

Keywords
  • Amino Acid Sequence
  • Animals
  • Chickens
  • Computer Simulation
  • Egg Proteins/*chemistry/*metabolism
  • Histocompatibility Antigens Class II/*chemistry/*metabolism
  • Macromolecular Substances
  • Mice
  • Models, Molecular
  • Muramidase/*chemistry/*metabolism
  • Peptide Fragments/*chemistry/*metabolism
  • Protein Binding
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • T-Lymphocytes/metabolism
Affiliation Not a UNIGE publication
Citation (ISO format)
WEBER, P. et al. Molecular modeling of hen egg lysozyme HEL[52-61] peptide binding to I-A(k) MHC class II molecule. In: International immunology, 1998, vol. 10, n° 12, p. 1753–1764. doi: 10.1093/intimm/10.12.1753
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ISSN of the journal0953-8178
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