Glycine-alanine repeats impair proper substrate unfolding by the proteasome.

ABSTRACT: Proteasome ATPases unravel folded proteins. Introducing a sequence containing only glycine and alanine residues (GAr) into substrates can impair their digestion. We previously proposed that a GAr interferes with the unfolding capacity of the proteasome, leading to partial degradation of products. Here we tested that idea in several ways. Stabilizing or destabilizing a folded domain within substrate proteins changed GAr-mediated intermediate production in the way predicted by the model. A downstream folded domain determined the sites of terminal proteolysis. The spacing between a GAr and a folded domain was critical for intermediate production. Intermediates containing a GAr did not remain associated with proteasomes, excluding models whereby retained GAr-containing proteins halt further pr

SUBMITTER: Hoyt MA 

PROVIDER: S-EPMC1440830 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature