AAA ATPases

By Jennifer McDowall

Protein degradation within a cell is essential for protein turnover, for regulatory control, and for quality control to remove incorrectly folded or damaged proteins. However, a cell must be able to tightly regulate which proteins are degraded to avoid removing proteins vital to cellular function, and to cope with the ever-changing protein requirements within cells. The proteasome is responsible for selective protein degradation within cells, degrading only those proteins that are marked for destruction. The proteins targeted are often short-lived molecules, such as regulatory proteins that are controlled in part through rapid synthesis and degradation. Proteins are selected for degradation by the proteasome through an ubiquitin-tagging system, a highly regulated process whereby a chain of small ubiquitin proteins are covalently attached to a condemned protein. However, some proteins can be degraded by proteasomes without the ubiquitin tag.

The breakdown of proteins by proteasomes is an ATP-dependent process. Proteasomes make use of a specialised family of ATPases known as AAA ATPases (ATPases Associated with various cellular Activities).

AAA ATPases, Driving Selective Protein Degradation.

There are many types of ATPases, all of which work to harness energy gained from breaking a phosphate bond. AAA ATPases are a special family of ATPases, where the binding and hydrolysis of ATP acts as a switch between two conformational states. AAA ATPases are usually arranged in multimeric assemblies, where the conformational changes from ATP-binding and hydrolysis can be propagated through the assembly to create an efficient molecular motor that acts upon a target substrate, either translocating or remodelling the substrate. AAA ATPases are essential for many cellular processes, including cell cycle, signal transduction and regulation of gene expression.

Proteasomes make use of AAA ATPases for breaking down proteins. In eukaryotes, six distinct AAA ATPases form a hexameric ring that acts as a chaperone to unfold and de-ubiquitinate tagged proteins prior to threading them through the proteasome for digestion. It appears that the different AAA ATPases within a proteasome aid in the recognition and degradation of different subsets of proteins.

Next: Protein digestion in the Proteasome