The role of an unstructured region in the proteasome inhibition

We have investigated how the misfolded proteins in various neurodegenerative diseases inhibit the protein degradation by the proteasome. We found that an unstructured region of the misfolded protein directly interacts with the proteasome, which causes the competitive inhibition of the degradation of natural proteasome substrates and the disassembly of the 19S proteasome complex.