The ubiquitinproteosome pathway

A central mechanism in the degradation of cytoplasmic and nuclear proteins uses the small protein ubiquitin. This globular protein contains 76 amino acids (molecular mass, 8.5 kDa) and is ubiquitous in the eukaryotes. Its structure is highly conserved and very stable in a range of conditions. Its function is to mark proteins for degradation, which it does via two key features, a C-terminal tail (Arg-Gly-Gly) and a lysine residue at position 48. Proteins destined for breakdown are conjugated to ubiquitin in a ligase reaction involving ATP at the carboxy terminal tail. The target protein may then be modified by the binding of several more ubiquitins, resulting in a polyubiquitin chain to be degraded at the proteosome.

Proteosomes are large protein complexes (molecular mass 2,000 kDa) found in the nucleus and cytoplasm of all plant cells, where they function to degrade proteins. They are composed of a Core Particle and two Regulatory Particles (Figure 14.1). The Core Particle (CP) is constructed of 14 different proteins assembled in groups of 7, each group

Figure 14.1 Simplied structure of the proteosome.

forming a ring. Four rings are arranged in stacks. There is a Regulatory Particle (RP) at each end of the CP made of 14 different proteins, some of which are ATPases and others that recognise poly-ubiquitin. The target protein is unfolded by the ATPases in the RP and the ubiquitins are released for reuse. The protein moves into the central cavity of the CP where specific proteases on the interior surface degrade the protein releasing peptides of about eight amino acids long.

A good example of how this pathway may control a physiological process involves the role of the cyclins in the cell cycle (Chapter 10). This family of proteins is involved in the cell cycle, where their concentrations are crucial. They accumulate during G1. S and G2 phases, and when a critical concentration is reached, they initiate mitosis by binding to and activating the cdc2 protein kinase. During metaphase the cyclins are rapidly degraded, reducing the pool of active cdc2 protein kinase, thereby preventing newly formed daughter cells from entering into another phase of mitosis. Once the cyclin pool declines, degradation ceases, and cyclin concentrations being to rise again, initiating another round of the cell cycle. Clearly, interference with cyclin synthesis and degradation will have a profound effect on the cell cycle and is a potential target for herbicide development.

Was this article helpful?

0 0
Brand Spanking New Detoxify

Brand Spanking New Detoxify

How To Safely Detoxify Your Body And Revitalize. Here's A Step-By-Step Plan To GetA Proper Mindset, Get Positive,And Most Of All... Find Your Special, Customized Detox Plan.

Get My Free Ebook

Post a comment