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Immunogenetics

, Volume 55, Issue 7, pp 437–449 | Cite as

Bioinformatic analysis of functional differences between the immunoproteasome and the constitutive proteasome

  • Can KesmirEmail author
  • Vera van Noort
  • Rob J. de Boer
  • Paulien Hogeweg
Original Paper

Abstract

Intracellular proteins are degraded largely by proteasomes. In cells stimulated with gamma interferon , the active proteasome subunits are replaced by "immuno" subunits that form immunoproteasomes. Phylogenetic analysis of the immunosubunits has revealed that they evolve faster than their constitutive counterparts. This suggests that the immunoproteasome has evolved a function that differs from that of the constitutive proteasome. Accumulating experimental degradation data demonstrate, indeed, that the specificity of the immunoproteasome and the constitutive proteasome differs. However, it has not yet been quantified how different the specificity of two forms of the proteasome are. The main question, which still lacks direct evidence, is whether the immunoproteasome generates more MHC ligands. Here we use bioinformatics tools to quantify these differences and show that the immunoproteasome is a more specific enzyme than the constitutive proteasome. Additionally, we predict the degradation of pathogen proteomes and find that the immunoproteasome generates peptides that are better ligands for MHC binding than peptides generated by the constitutive proteasome. Thus, our analysis provides evidence that the immunoproteasome has co-evolved with the major histocompatibility complex to optimize antigen presentation in vertebrate cells.

Keywords

Proteasome MHC class I epitopes Antigen-processing, presentation Specificity Co-evolution 

Notes

Acknowledgements

We thank Alexander K. Nussbaum for discussing the analysis. The diversity measure used here was derived by Nigel Burroughs. We are grateful to S.M. McNab for linguistic advice.

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Can Kesmir
    • 1
    • 2
    Email author
  • Vera van Noort
    • 1
    • 3
  • Rob J. de Boer
    • 1
  • Paulien Hogeweg
    • 1
  1. 1.Theoretical Biology/BioinformaticsUtrecht UniversityUtrechtThe Netherlands
  2. 2.Center for Biological Sequence Analysis, BioCentrum-DTUTechnical University of DenmarkLyngbyDenmark
  3. 3.Center for Molecular and Biomolecular InformaticsNijmegen Center for Molecular Life SciencesNijmegenThe Netherlands

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