1. Protein stability, protein-protein interactions
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Protein stability, protein-protein interactions
Protein stability
- how proteins achieve stability under extreme conditions (class presentation)
Protein-protein interactions
- recent literature (presentations)

2. Stabilization/destabilization forces affecting proteins
11-2
Any of the forces/structures below could be stabilizing or destabilizing:
hydrophobic…………… increased strength at higher temperatures
H-bond…………………. mostly stabilizing; could decrease flexibility
ionic…………………….. can be attractive or repulsive
surface residues………. major contribution to protein stability
internal residues………. major contribution to protein stability
compactness………….. can affect stability or flexibility
loops……………………. short loops increases stability at higher temperatures
cavities…………………. presence and size can affect stability
secondary structures…. e.g., β-sheets, α-helices more stable than coils
quaternary structures… oligomeric structures can be more stable (esp. hetero.)
ligand binding…………. e.g., nucleotides, cofactors, etc.
membrane binding…… major effect(s) on protein stability
protein modifications…. modulation of conformation, activity, stability, location
others…………………... temperature, pH, salt, small molecules, pressure, etc.

3. Protein stability in different organisms
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Protein stability in different organisms
Terminology
psychrophile
mesophile
thermophile
hyperthermophile
halophile
acidophile
barophile
extremophiles
cold-adapted; cold-loving (-2 ºC to ~15ºC)
grows at moderate temperatures (~15ºC to ~45ºC) and conditions
heat-loving; grows at >45ºC up to ~80ºC
grows at >80ºC; limit so far is about 115ºC
grows at high in concentrated salts (internal >1M!)
grows under highly acidic conditions, i. e., ~ pH 0-pH 2)
adapted to high pressures (e.g., underwater)
those that grow under extreme conditions
.....

4. Surface residues: stability vs instability
11-4
thermophilic
- Mesophilic Bs-CspB and thermophilic Bc-Csp differ at 12 positions in 67 aa
- variants at all positions were constructed and tested for stability
Cold shock protein (Csp) from Bacillus caldolyticus. Perl et al. (2000) Nat. Struct. Biol. 7, 380.
thermophilic CspB
mesophilic CspB
increased stability
decreased stability
thermophilic
mesophilic

5. Protein biogenesis/degradation machineries in extremophiles
11-5
Question: how do organisms survive at extreme temperatures? Do they have more proteins devoted to protecting the organism, e.g.,
molecular chaperones?
protein folding catalysts?
proteases?
Answer: the short answer is ‘it doesn’t appear to be the case’
intrinsic property of proteins

6. protein-protein interactions
11-6
“Here one should remember that any protein fails to execute its function unless it interacts with other biomolecules”
- Takashi et al. (2001) Proc. Natl. Acad. Sci. USA 98, 4569.