9.2 Protein Dynamics and Protein Folding

Mechanism of protein folding

remains a mystery

Protein folding is a ___ ____ ____ process

massively parallel sorting

Protein folding is apt to resemble

RNA folding

Protein stability depends on the balance of three factors

1. unfavorable conformational entropy (delta S is negative) change → folding

2. favorable enthalpy (delta H is negative) from intramolecular noncovalent interactions

3. favorable entropy (delta S is positive) from burying hydrophobic residues in water

Energy well

proteins have a sequence and have no choice but to fold due to the loss of free energy

van der Waals interactions operate over

short distances (attractive force is proportional to distance ^-6

van der Waals result from the overlap of

short lived, highly fluctuating dipoles of nonbonding electron orbitals

Inside the densely packed protein interior, numerous van der Waals interaction sum up and contribute to the

stability of a folded protein

Hydrogen bonding is/is not a driving force for protein folding because H-bonds with water are broken to make intramolecular H-bonds

IS NOT

Formation of extended H-bond networks (especially in a-helices or B-sheets) compensate for

loss of AA-water bonds, so H-bonding changes do not effect free energy much

Contribution of noncovalent interactions, particularly hydrogen bonding, to enthalpy of folding is offset by

protein folding decreases interactions between the protein and water

Hydrophobic interactions is a major contribution to

protein folding and stability; water around unfolded protein is ordered and structured

Proteins fold with hydrophobic residues on the

interior

Protein folding increases entropy of the

protein-water system because water is less ordered (delta S is positive)

Once a protein folds, the protein structure can be stabilized by the formation of

disulfide (-S-S-) bonds between sulfhydryls (-SH) of cysteine

Proteins can be

denatured or unfolded

Renaturation

Some proteins can spontaneously refold into native 3D structure

Ribonuclease A (right) can be ____ and ____

denatured and renatured

Chaperonins

helper proteins that “assist” polypeptide folding into native structure (or prevent improper folding or aggregation)

Spongiform encephalopathy AKA

mad cows disease

Prion diseases

proteinaceous infectious only and is found int he central nervous system

Function of normal prions PrP^c is

unknown

Aberrant prions PrP^Sc have a…

different fold (misfolded)

PrP^Sc can nucleate alternate

folding in PrP^C

PrP^Sc believed to be the caustitiveagents of

spongiform encephalopies (neurodegenerative disorders)