The structure of the mammalian 20S proteasome at 2.75 Å resolution

The 20S proteasome is the catalytic portion of the 26S proteasome. Constitutively expressed mammalian 20S proteasomes have three active subunits, beta1, beta2, and beta5, which are replaced in the immunoproteasome by interferon-gamma-inducible subunits beta1i, beta2i, and beta5i, respectively. Here we determined the crystal structure of the bovine 20S proteasome at 2.75 Angstrom resolution. The structures of alpha2, beta1, beta5, beta6, and beta7 subunits of the bovine enzyme were different from the yeast enzyme but enabled the bovine proteasome to accommodate either the constitutive or the inducible subunits. A novel N-terminal nucleophile hydrolase activity was proposed for the beta7 subunit. We also determined the site of the nuclear localization signals in the molecule. A model of the immunoproteasome was predicted from this constitutive structure.