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Control of Cellular Processes & Cell Differentiation
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Biochemistry - 8 lectures Molecular biology - 10 lectures
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BiochemistryLecture 1 - introduction / principles of signaling
Continuously needed signals
- survive
- grow+divide
- differentiate
paracrine = direct but doesn’t require
contact
endocrine = via blood vessels
→ specificity needed
synaptic
→ sensitivity needed, no specificity
Different types of signaling
➢ Way of signaling
→ transcription is very slow
➢ Type of receptors
○ intracellular receptors = receives signals that can pass through membranes
○ cell-surface receptors = is on membrane, since signal cannot pass through
membrane
➢ Effect
○ same signal can have a different effect depending on the cell type
, ➢ Response
→ hard to tell the difference when
measuring at population level vs cell level
○ gradually
○ abruptly
cells can respond differently to
concentration differences of the same
molecule
Interactions
- Electrostatic interactions
- H-bonds
- van der Waals interactions
- Hydrophobic interactions
Energy
ΔG = free energy difference products - substrates
Allostery
➢ allosteric enzyme
= enzyme that can be in two states, active and inactive
○ inactive = cannot bind substrate
○ This way different signals can be perceived and integrated by the same
protein
➢ allosteric inhibitors
= binds to enzyme, making it unstable and therefore inactive
➢ allosteric proteins
= molecule caused fundamental structural change, alters its ability to react with that
particular type of molecule in the future
➢ allosteric transition
= transitional stage of a changing of structure in a proteins
,Covalent modification of proteins
- fast
- reversible
- less energy needed than with production / degradation
Affects:
- collar location
- interactions with other proteins
- degradation
- activity
Examples
- phosphorylation
- acetylation
- Myristoylation
- Farnesylation = generation of a membrane anchor
- Ubiquitin → tags proteins for destruction, 4 linked ubiquitin molecules
Phosphorylation
done by protein kinases → kinases can be allosterically controlled
1. 2 strong negative charges are added
2. Directional new H bonds
3. Due to large change in free energy equilibria can change 10,000 fold
4. Very fast kinetics
5. Large rate of amplification possible
6. ATP as common phosphoryl group is linked to energy status
7. Reversible
, Lecture 2 & 3 - Components of signaling & Modules
Enzyme-coupled receptors
transmembrane receptors
- outside different for recognition of different molecules
- inside mostly kinases
EGF = epidermal growth factor
binding to receptor → dimerization arms are exposed
dimer is formed
kinases are activated
common interaction domains
- PH - Pleckstrin homology
- PTB - phosphotyrosine binding
- SH2/3 - Src homology 2/3 → P to tyrosine
- LRR - leucine rich repeat
phosphorylation of phospholipid by a kinase can create binding site
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