Degradation (26S Proteasome)
In the collection of Dr. Alfred Goldberg, Professor of Cell Biology, Harvard Medical School
27" h x 13" w
The (26S) Proteasome.
Order / Disorder. The Big Bang - creation of the universe = order. What follows - disorder?
For life forms, growth and division represent order.
The ubiquitous subcellular structure known as the proteasome is responsible for disorder - for breaking down abnormal and unfolded proteins (and eventually, all proteins) into short non-functional pieces. In vertebrates, these short pieces are transferred to "MHC" proteins which present them to the T cells of the immune system. In an infection, pieces of viral (or bacterial) proteins are seen as "foreign" by our T cells which then attack the virus.
Found in all cells, the organelle (cell structure) known as the proteasome constantly degrades our proteins - especially abnormal and unfolded proteins. This organelle was named by Goldberg who also pioneered development of Velcade, a proteasome inhibitor used to treat half a million patients with multiple myeloma, a form of cancer.
In this representation, an unfolded protein is brought by ubiquitin protein (white) to the proteasome, enters its barrel-shaped cavity and is cleaved at 6 catalytic sites (red) into small pieces. These short pieces of the protein emerge from the proteasome and are transferred to MHC proteins which present them to the T cells of the immune system. T cells which recognize these pieces as "self" remain quiescent. In an infection; however, viral or bacterial proteins degraded by the proteasome yield pieces seen as "foreign" by our T cells, which then mount a strong and protective immune response. Work leading to an understanding of this process led to the 2004 Nobel Prize in Chemistry for Ciechanover, Hershko, and Rose.
In the collection of Dr. Alfred Goldberg, Dept. of Cell Biology, Harvard Medical School.
An image of this work (in triplicate) appears on the cover of the Oct 1, 2017 issue of The Biochemical Journal.