Lecture 18 - 021611

Lecture 18 - 021611 - Lecture 18 Protein Degradation 1 Must...

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1 Lecture 18 Protein Degradation
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2 Must obtain from diet
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3 Digestion of dietary proteins Pepsin, prefer acidic environment in stomach
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7 Regulated Degradation: Ubiquitin-Proteasome System Aaron Ciechanover Avram Hershko Irwin Rose Nobel Prize in Chemistry, 2004 Alex Varshavsky Only 3 people can win the Nobel Prize …
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8 Poly-ubiquitin (Usually Lys-48 one ubiquitin to C-terminus of another) •76 residues, highly conserved •C terminus attached to Lys in the protein to be degraded Ubiquitin
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9
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10 Regulated Degradation: Ubiquitin-Proteasome System Sulfhydryl group of a Cys in E1 ATP driven E1 — Ubiquitin Activating Enzyme E2 — Ubiquitin Conjugating Enzyme E3 — Ubiquitin Protein Ligase
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12 Which proteins are degraded? By the amino-terminal residue (N-terminal rule) Met ~20 hours half life Arg ~2 minutes half life Amino acid sequence PEST (Pro, Glu, Ser, Thr) E3 are readers of the N-terminal residues
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14 Proteasome 26S proteasome (20S core + 2 19S caps)
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16 Attacks the
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Lecture 18 - 021611 - Lecture 18 Protein Degradation 1 Must...

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