Degradation (26S Proteasome)
2015
In the collection of Dr. Alfred Goldberg, Professor of Cell Biology, Harvard Medical School
Stained glass
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.
Scientific Background:
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.
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In the collection of Dr. Alfred Goldberg, Dept. of Cell Biology, Harvard Medical School.
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An image of this work (in triplicate) appears on the cover of the Oct 1, 2017 issue of The Biochemical Journal.
http://www.biochemj.org/content/474/19.cover-expansion