1aqd Citations

The class II MHC protein HLA-DR1 in complex with an endogenous peptide: implications for the structural basis of the specificity of peptide binding.

Structure 5 1385-96 (1997)
Cited: 12 times
EuropePMC logo PMID: 9351812

Abstract

Background

Class II major histocompatibility complex (MHC) proteins are cell surface glycoproteins that bind peptides and present them to T cells as part of the mechanism for detecting and responding to foreign material in the body. The peptide-binding activity exhibits allele-specific preferences for particular sidechains at some positions, although the structural basis of these preferences is not understood in detail. We have determined the 2.45 A crystal structure of the human class II MHC protein HLA-DR1 in complex with the tight binding endogenous peptide A2 (103-117) in order to discover peptide-MHC interactions that are important in determining the binding motif and to investigate conformational constraints on the bound peptide.

Results

The bound peptide adopts a polyproline II-like conformation and places several sidechains within pockets in the binding site. Bound water molecules mediate MHC-peptide contacts at several sites. A tryptophan residue from the beta 2 'lower' domain of HLA-DR1 was found to project into a pocket underneath the peptide-binding domain and may be important in modulating interdomain interactions in MHC proteins.

Conclusion

The peptide-binding motif of HLA-DR1 includes an aromatic residue at position +1, an arginine residue at position +2, and a small residue at position +6 (where the numbering refers to the normal MHC class II convention); these preferences can be understood in light of interactions observed in the peptide-MHC complex. Comparison of the structure with that of another MHC-peptide complex shows that completely different peptide sequences bind in essentially the same conformation and are accommodated with only minimal rearrangement of HLA-DR1 residues. Small conformational differences that are observed appear to be important in interactions with other proteins.

Articles - 1aqd mentioned but not cited (12)

  1. IMGT, the international ImMunoGeneTics information system: a standardized approach for immunogenetics and immunoinformatics. Lefranc MP. Immunome Res 1 3 (2005)
  2. Predictions versus high-throughput experiments in T-cell epitope discovery: competition or synergy? Lundegaard C, Lund O, Nielsen M. Expert Rev Vaccines 11 43-54 (2012)
  3. Identification of HLA-DRPhebeta47 as the susceptibility marker of hypersensitivity to beryllium in individuals lacking the berylliosis-associated supratypic marker HLA-DPGlubeta69. Amicosante M, Berretta F, Rossman M, Butler RH, Rogliani P, van den Berg-Loonen E, Saltini C. Respir. Res. 6 94 (2005)
  4. Mapping the HLA-DO/HLA-DM complex by FRET and mutagenesis. Yoon T, Macmillan H, Mortimer SE, Jiang W, Rinderknecht CH, Stern LJ, Mellins ED. Proc. Natl. Acad. Sci. U.S.A. 109 11276-11281 (2012)
  5. Prediction of the binding affinities of peptides to class II MHC using a regularized thermodynamic model. Bordner AJ, Mittelmann HD. BMC Bioinformatics 11 41 (2010)
  6. Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study. Chen PL, Shih SR, Wang PW, Lin YC, Chu CC, Lin JH, Chen SC, Chang CC, Huang TS, Tsai KS, Tseng FY, Wang CY, Lu JY, Chiu WY, Chang CC, Chen YH, Chen YT, Fann CS, Yang WS, Chang TC. Nat Commun 6 7633 (2015)
  7. A relation between the principal axes of inertia and ligand binding. Foote J, Raman A. Proc. Natl. Acad. Sci. U.S.A. 97 978-983 (2000)
  8. Prediction of epitope-based peptides for the utility of vaccine development from fusion and glycoprotein of nipah virus using in silico approach. Sakib MS, Islam MR, Hasan AK, Nabi AH. Adv Bioinformatics 2014 402492 (2014)
  9. An effective and effecient peptide binding prediction approach for a broad set of HLA-DR molecules based on ordered weighted averaging of binding pocket profiles. Shen WJ, Zhang S, Wong HS. Proteome Sci 11 S15 (2013)
  10. Prediction of an Epitope-based Computational Vaccine Strategy for Gaining Concurrent Immunization Against the Venom Proteins of Australian Box Jellyfish. Alam MJ, Ashraf KU. Toxicol Int 20 235-253 (2013)
  11. An automated framework for understanding structural variations in the binding grooves of MHC class II molecules. Yeturu K, Utriainen T, Kemp GJ, Chandra N. BMC Bioinformatics 11 Suppl 1 S55 (2010)
  12. Computational Identification and Characterization of a Promiscuous T-Cell Epitope on the Extracellular Protein 85B of Mycobacterium spp. for Peptide-Based Subunit Vaccine Design. Hossain MS, Azad AK, Chowdhury PA, Wakayama M. Biomed Res Int 2017 4826030 (2017)




Related citations provided by authors (3)

  1. Three Dimensional Structure of a Human Class II Mhc Protein Hla-Dr1 Bound to an Endogenous Peptide. Murthy VL Thesis - (1996)
  2. Crystal Structure of the Human Class II Mhc Protein Hla-Dr1 Complexed with an Influenza Virus Peptide. Stern LJ, Brown JH, Jardetzky TS, Gorga JC, Urban RG, Strominger JL, Wiley DC Nature 368 215- (1994)
  3. Three-Dimensional Structure of the Human Class II Histocompatibility Antigen Hla-Dr1. Brown JH, Jardetzky TS, Gorga JC, Stern LJ, Urban RG, Strominger JL, Wiley DC Nature 364 33- (1993)