Proteasome
Ubiquitin proteasome system or ubiquitin-26S proteasome system, is a barrel-shaped multi-Protein complex that can specifically digest other proteins into short polypeptides and amino acids in an ATP-driven reaction. The Ubiquitin proteasome system is essential for many cellular processes including Cell cycle, Signal transduction and regulation of Gene expression. The importance of proteolytic degradation inside cells and the role of Ubiquitin in proteolytic pathways was acknowledged in the awarding of the 2004 Nobel Prize in Chemistry to Aaron Ciechanover, Avram Hershko and Irwin Rose.
Importance of the ubiquitin proteasome system
Ubiquitin proteasome system is the primary mechanism in eukaryotic cells for degrading unwanted and misfolded protein. Through the cascade of E1 ubiquitin activating, E2 ubiquitin conjugating, and E3 ubiquitin ligase enzymes, Ubiquitin monomers are attached sequentially to the target proteins The polyubiquitinated proteins are then recognized by the 26S proteasome, a large ATP-dependent multicatalytic Protease, which removes the ubiquitin chain and degrades the proteins to short peptides. The selection and specific timing of polyubiquitination of the target proteins are conferred by different E3 ubiquitin ligases. The Ubiquitin proteasome system is essential for many cellular processes including Cell cycle, Signal transduction and regulation of Gene expression. In plants it is also involved circadian clocks, or phytohormones signaling pathways. Cell cycle progression is controlled by ordered action of cyclin-dependent kinases (CDKs), activated by defined cyclins, appearing for given periods in the cycle. When the function of a CDK-cyclin complex is accomplished, the associated cyclin partner becomes polyubiquitinated and destroyed by the ubiquitin-26S proteasome system. The irreversible nature of proteolysis is utilized by cells to give the cell cycle directionnality. In the cell cycle, two structurally related multicomponent ubiquitin ligases, the Anaphase-promoting complex (APC) and the Skp1/Cul1/F-box protein (SCF) complexes (SCF complex) have essential and complementary functions by temporally controlled degradation of various cell cycle proteins. In plants, Auxin signaling is mediated by auxin-induced degradation of the Aux/IAA proteins by SCFTIR1, where TIR1 is an auxin receptor.Structure of the 26S proteasome
The 26S proteasome is used for the digestion of Ubiquitin-marked proteins. It is a barrel-shaped multi-Protein complex that can specifically digest other proteins into short polypeptides and amino acids in an ATP-driven reaction. The proteasome is hollow, providing an enclosed space for protein digestion, and has openings at the two ends to allow entry of the targeted protein. It is located on both sides of a cell's nuclear membrane and consists of a 20S core protease particle and two 19S regulatory particles. The 20S unit consists of 2 rings of α subunits and 2 rings of β subunits, stacked in the order αββα as a series of heptomeric rings. It is about 15 nm long and 11.5 nm wide. The alpha subunits are structural, while three of the beta subunits are catalytic. In mammals, different catalytic subunits exist and are induced or repressed by cytoskines such as interferon; the different beta subunits alter the cleavage and length preferences of the proteasome.Each 19S unit consists of a lid and a base with a 19S regulatory particle is attached to each end of the 20S core particle via its base. Some of the subunits in the base are ATPases.
The core 20S proteasome associated with different caps, including the PA28 complex; these different caps modify the activity of the proteasome.