Animals with immune systems have two types of proteasomes, "standard proteasomes" and "immunoproteasomes" that respectively contain constitutively expressed catalytic subunits or interferon-gamma-inducible catalytic subunits. Interestingly, proteasome assembly is biased against formation of most mixed proteasomes containing combinations of standard subunits and immunosubunits. We previously demonstrated that catalytic subunit propeptide differences contribute to this assembly specificity. In the current study, we investigated the contributions of catalytic subunit propeptides and C-terminal extensions to intra-proteasome protein-protein interactions that are potentially involved in mediating biased assembly of human proteasomes, and we found a number of interactions that differentially depended on these structures. For example, the C-terminal extension of standard subunit beta 2 is required for beta 2's interaction with adjacent beta 3, whereas the C-terminal extension of immunosubunit beta 2i is dispensable for beta i's interaction with beta 3. Taken together, our results suggest mechanisms whereby differential intra-proteasome interactions could contribute to proteasome assembly specificity. (C) 2007 Elsevier Inc. All rights reserved.