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