Proteasome Research

PROTEASOME - a novel protein digesting "organelle?"
     an enzyme complex of non-lysosomal proteins that degrade endogenous proteins (proteins synthesized within cell) such as transcription factors, cell cycle cyclins, virus coded proteins, improperly folded proteins due to translation errors & made by faulty genes, and proteins damaged by cytosol molecules. Cystic fibrosis is due to the accelerated degradation of Cl transporter protein. Proteasomes degrade proteins to short peptides for further hydrolysis by cytoplasmic exopeptidases
     Discovered by
Alfred Goldberg & Martin Rechsteiner in 1980's proteasomes are
large multi-enzyme complexes (see fig.) Average human cell holds about 20,000 proteasomes.
     
Protein Digestion...
begins when cells add small polypeptide (ubiquitin- a globular protein of 76 aa with virtually identical aa sequence in bacteria, yeast, or mammals) to a protein to be digested. 3 enzymes of cells [ E1, E2, E3 ] add Ubiquitin to proteins which targets a protein's entry in a Proteasome complex.
    Each proteasome is a
barrel shaped complex (2,400kD) made of 4 parts: 1) a Lid of 9 proteins, 2) a Regulatory Cap that lets in only ubiquitinized proteins, 3) a Base of 4 stacked protein rings with protease activities, and 4) a Base Cap.