MHC-linked LMP gene products specifically alter peptidase activities of the proteasome (original) (raw)

Nature volume 365, pages 262–264 (1993)Cite this article

Abstract

PROTEASOMES are highly conserved macromolecular structures which function as endopeptidases1–3. They are found in the cyto-plasm and nucleus of eukaryotic tissues and consist of at least 14 non-identical subunits with molecular masses ranging from ∼20 to 32K. Proteasomes are essential in the selective degradation of ubiquitinated and certain non-ubiquitinated proteins, acting as the proteolytic core of an energy-dependent 26S (1,500K) proteolytic complex. Two proteasome subunits, LMP2 and LMP7 (refs 4–7), are encoded within the major histocompatibility complex (MHC), implicating proteasomes in antigen processing8,9. Here we deter-mine the function of these two MHC-linked subunits by comparing the proteolytic activities of purified proteasomes containing (LMP+) or lacking (LMP−) these components. We find that pro-teasomes of both types have endopeptidase activity against sub-strates bearing hydrophobic, basic or acidic residues immediately preceding the cleavage site (the PI position) and at sites following asparagine, glycine and proline residues. The activity of LMP+ proteasomes is much higher than that of LMP− proteasomes against substrates with hydrophobic, basic or asparagine residues at PI, whereas their activities are comparable when acidic and glycine residues are present at PI. The MHC-linked LMP2 and LMP7 subunits therefore function to amplify specific endopeptid-ase activities of the proteasome.

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Authors and Affiliations

  1. Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, Massachusetts, 02115, USA
    James Driscoll & Daniel Finley
  2. Department of Microbiology and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, 23298–0678, USA
    Michael G. Brown

Authors

  1. James Driscoll
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  2. Michael G. Brown
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  3. Daniel Finley
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  4. John J. Monaco
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Driscoll, J., Brown, M., Finley, D. et al. MHC-linked LMP gene products specifically alter peptidase activities of the proteasome.Nature 365, 262–264 (1993). https://doi.org/10.1038/365262a0

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