The 26S proteasome is one of the principal cellular machines for degrading proteins. Proteins to be destroyed are marked with tags in the form of the small protein ubiquitin, and when the proteasome encounters such polyubiquitinated proteins, it catches, then degrades them. The proteasome has, not one, but at least two hands with which it latches on to its ubiquitinated prey.
The ubiquitin-proteasome system controls almost all cellular processes — such as progres¬sion through the cell-division cycle and signal transduction, by degrading regulatory proteins. The destruction of a protein begins with covalent tagging with a chain consisting of several copies of ubiquitin, through the concerted action of a cascade of enzymes. Principally, polyubiquitin chains that consist of up to four or more ubiquitin molecules , promote degradation by the 26S proteasome. This protein is a multi-catalytic enzyme, with a highly ordered structure that is composed of at least 33 different subunits arranged in two sub-complexes, a 20S core particle and one or two 19S regulatory particles. The protein-degrading sites lie inside the core particle. Substrate proteins must be unfolded to reach the protein degrading sites
Protein substrates are marked for degradation by polyubiquination which occurs with E1 ( activating ), E2 ( conjugating ) and E3 (ligating ) enzymes. The process can be reversed,. If not reversed the ubiquitinated units are recognised by the 26S protein degrading machine by two intrinsic receptors Rpn10 and RPn13.
Saeki and Tanaka 2008, Two hands for degradation Nature vol 453 pp 460-61
- Martin Eastwood