This class: Regulation of protein activities (1) What is a protein activity? (2) How to change the rate of a specific cellular activity? (3) Rapid vs slower change (4) Varying amount vs specific activity of a protein (5) Coordinating simultaneous changes in related proteins (6) How to achieve fine/differential regulation
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This class: Regulation of protein activities (1) What is a protein activity? (2) How to change the rate of a specific cellular activity? (3) Rapid vs slower.
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This class:
Regulation of protein activities
(1) What is a protein activity?(2) How to change the rate of a specific cellular activity?(3) Rapid vs slower change(4) Varying amount vs specific activity of a
protein(5) Coordinating simultaneous changes in
related proteins(6) How to achieve fine/differential regulation
What is meant by a protein activity?
Overall cellular activity vs specific activity
Specific activity of a protein = amount of event performed per unit time per molecule of that protein
Overall activity of a protein = amount of event per unit time per cell (or unit tissue mass)
Regulation of protein function
How to change the rate of a protein’s overall cellular activity?
(1) Change specific activity of that protein(2) Change amount of that protein
Important additional considerations:
(1) What rate of change is required?(2) Do activities of any other proteins need to be changed simultaneously?
Post-translational regulation of protein function
• Affects existing proteins (does not ∆ amt, but ∆ specific activity)• Can be rapid• Can be short- or long-lived• Multiple proteins may be affected• Multiple modifications are possible within a protein
Post-translational regulation
1. Reversible phosphorylation
the first example (historically): mobilization of glucose from glycogen
Sugar stored in skeletal muscle and liverPolymer of glucoseThe enzyme glycogen phosphorylase releases individual subunits of glucose from the polymer
Glycogen phosphorylase
How to control glycogen phosphorylase so it catalyzes this reaction only when necessary?
Glycogen phosphorylase - P
ATP
ADP
Phosphorylasekinase
Glycogen phosphorylase - P
Phosphoproteinphosphatase
Protein phosphorylation: a ubiquitous strategy
ATP cleaved to ADP; the P released covalently attached to a protein
Phosphorylation is often of just a single amino acid residue :
SerineTyrosineThreonine
Reversible protein phosphorylation: a widespread regulatory strategy
Post-translational regulation
2. Other chemical modifications of individual amino acids
- egs. reversible acetylation, hydroxylation
- Use of mass spectrometry to identify prosthetic groups:
Post-translational regulation
3. Cleavage of an internal domain
Post-translational regulation
3. Cleavage of internal domain
Pro-caspase-3 activated to caspase-3 to initiate apoptosis
Post-translational regulation
4. Movement between subcellular compartments
Post-translational regulation
4. Movement between subcellular compartments
Post-translational regulation
5. Reversible association-dissociation
Heat shock factor-1 (HSF-1)
Post-translational regulation
6. Modification of immediate environment- eg. oxidation of cardiolipin causes
cytochrome c release
• Post-translational modifications change specific activity of proteins
• Only change the absolute amount of proteins secondarily (because transcription factors may also be reversibly phosphorylated)
Regulation by altering absolute amount of a protein
Regulation by altering absolute amount of a protein