IMMUNOPROTEASOME ASSEMBLY - COOPERATIVE INCORPORATION OF INTERFERON-GAMMA (IFN-GAMMA)-INDUCIBLE SUBUNITS

LMP2, LMP7, and MECL are interferon gamma-inducible catalytic subunits of vertebrate 20S proteasomes, which can replace constitutive catalyt ic subunits (delta, X, and Z, respectively) during proteasome biogenes is. We demonstrate that MECL requires LMP2 for efficient incorporation into preproteasomes, and preproteasomes containing LMP2 and MECL requ ire LMP7 for efficient maturation. The latter effect depends on the pr esequence of LMP7, but not on LMP7 catalytic activity. This cooperativ e mechanism favors the assembly of homogeneous ''immuno-proteasomes'' containing all three inducible subunits, suggesting that these subunit s act in concert to enhance proteasomal generation of major histocompa tibility complex class I-binding peptides.