Protein Degradation
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Proteasome
Size: 33nm
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Proteasome
Ubiquitin
The PEST sequence is an example of a degradation signal:
It is rich in proline (P), glutamic acid (E), serine (S), and threonine (T).
The N-end Rule
Yeast
N-terminal residues - approximate half-life of proteins in S. cerevisiae.
Met, Gly, Ala, Ser, Thr, Val, Pro - > 20 hrs (stabilizing)
Ile, Glu - approx. 30 min (stabilizing)
Tyr, Gln - approx. 10 min (destabilizing)
Leu, Phe, Asp, Lys - approx. 3 min (destabilizing)
Arg - approx. 2 min (destabilizing)
Bachmair A, Finley D, Varshavsky A (1986). Science. 234 (4773): 179–186.
Mammals
"N"-terminal residues - approximate half-life of proteins in mammals.
Val -> 100h
Met, Gly -> 30h
Pro -> 20h
Ile -> 20h
Thr -> 7.2h
Leu -> 5.5h
Ala -> 4.4h
His -> 3.5h
Trp -> 2.8h
Tyr -> 2.8h
Ser -> 1.9h
Asn -> 1.4h
Lys -> 1.3h
Cys -> 1.2h
Asp -> 1.1h
Phe -> 1.1h
Glu -> 1.0h
Arg -> 1.0h
Gln -> 0.8h
David K. Gonda; et al. (1989). Journal of Biological Chemistry. 264 (28): 16700–16712.
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Scientific American
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SUMO (small ubiquitin-related modifier)
Ruth Geiss-Friedlander & Frauke Melchior Nature Reviews Molecular Cell
Biology 8, 947-956 (December 2007)
Avram Hershko
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Avram Hershko
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Avram Hershko
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Avram Hershko
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