protein folding - rutgers universitycasegroup.rutgers.edu/lnotes/proteinfoldingb.pdf · protein...
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Protein Structure
Protein Structure
Central Dogma of Biology
Protein Folding in the Cell
The Hydrophobic Effect
The Hydrophobic Effectit drives binding
The Hydrophobic Effectit drives folding
Protein Structure
blue: hydrophobic
hydrophobic residues are buried
Protein FoldingProtein unfolding results in loss of function
Protein FoldingProtein unfolding results in loss of function
Ener
gy d
iffer
ence
~8-10 kcal mol-1
Protein FoldingProtein unfolding results in loss of function
Protein FoldingProtein (un)folding is highly cooperative
Protein FoldingHow does a protein arrive at its native structure?
The Levinthal’s paradox: a protein would take ~1077 years to fold
simulated folding pathway
Two folding models: the hierarchical and through the “molten globule”
Protein FoldingEnergy landscape
Protein FoldingEnergy landscape
Protein FoldingDeath by misfolding: the Prion diseases
Protein FoldingChaperones assist newly synthesized proteins to fold
Protein FoldingChaperones assist newly synthesized proteins to fold
Protein FoldingChaperones assist newly synthesized proteins to fold
The GroES-EL chaperonin
Protein Folding
One sequence, one fold
Anfinsen’s hypothesis: Sequence determines structure
Protein FoldingOne sequence, one fold?
PNAS, 2008, 105, 5057
Intrinsically Unstructured Proteins
Nat. Rev. Mol. Biol., 2005, 6, 199
Intrinsically Unstructured Proteins
Nat. Rev. Mol. Biol., 2005, 6, 199
Coupled folding and binding