Download Protein stability

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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)
Stabilization/destabilization forces
affecting proteins
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.
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Protein stability in different organisms
Terminology
psychrophile ..... cold-adapted; cold-loving (-2 ºC to ~15ºC)
mesophile ..... grows at moderate temperatures (~15ºC to ~45ºC) and conditions
thermophile ..... heat-loving; grows at >45ºC up to ~80ºC
hyperthermophile ..... grows at >80ºC; limit so far is about 115ºC
halophile ..... grows at high in concentrated salts (internal >1M!)
acidophile ..... grows under highly acidic conditions, i. e., ~ pH 0-pH 2)
barophile ..... adapted to high pressures (e.g., underwater)
extremophiles ..... those that grow under extreme conditions
Surface residues: stability vs instability
thermophilic
thermophilic CspB
- 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.
mesophilic CspB
increased stability
thermophilic
mesophilic
decreased stability
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Protein biogenesis/degradation
machineries in extremophiles
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 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
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protein-protein interactions
“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.