Relevance of the Non‐canonical Complex Formed by Proteasome Subunit α4

Abstract

The 20S proteasome plays an essential role in maintaining protein homeostasis as part of the larger 26S proteasome complex. It is composed of seven distinct α subunits and seven distinct β subunits arranged as a stack of four heptameric rings in an α7β7β7α7 manner. Assembly of these 28 subunits is very efficient and aided by assembly chaperones that function, in part, to prevent off‐pathway interactions. Certain α‐subunits of the proteasome form non‐canonical ring complexes in vitro. The significance of such complexes is not known but they could simply represent dead‐end, or off‐pathway, assemblies. We recently provided the first in vivo evidence of such a non‐canonical ring complex formed by the yeast α4 subunit. Levels of this complex increase when proteasome function is compromised. Here, we aim to further investigate the relevance of this α4 high molecular weight complex (α4HMWC). Using a salt bridge disruption strategy, we achieved destabilization of the α4HMWC without affecting proteasome assembly. If the α4 HMWCs are important physiologically, we may observe growth phenotypes of the resulting yeast mutant lacking this complex. Our results will help determine whether this complex is an off‐pathway, or dead‐end, product or whether it may have an independent function within the cell.Support or Funding InformationResearch Support Funds Grant from Indiana University‐Purdue University Indianapolis to A.R.KThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.