Protein Folding

Front 1

Unique property of the protein RNAase

Back 1

If you denature it, it will refold and become active again. It has 8 cystines that make 4 disulfide bonds.

Was also the first major experiment for protein folding.

Front 2

The experiment with RNAase used discovered what?

Back 2

That the native conformation of a protein is the most thermodynamically stable.

Proteins follow unique paths to get to native state.

Primary structure alone has the info for proper folding.

Front 3

Enthalpy

Back 3

delta H. measure of bond formation (-) or bond breaking (+)

Front 4

Entropy

Back 4

Delta S. A measure of increasing chaos (+) or decreasing chaos (-)

Front 5

Summary of Levintal's Paradox

Back 5

Proteins must have a process to their folding since to try every combination would take a period of time longer than the age of the universe.

Front 6

Globular protein folding is driven by what?

And how do we know?

Back 6

they are Entropy driven: the increased randomness of water

We know this because of the Heat Capacity (Cp)

When denatured, Cp increases,

when folded, Cp decreases.

Front 7

How do alcohols denature proteins?

Back 7

by making H-bonds with the protein and disrupting the structure.

Front 8

Fibrous protein folding is driven by what? and why?

Back 8

They are Enthalpy driven.

They are often made primarily of polar aa's that like to associate with water.

Front 9

What is the average free energy of folding?

Back 9

-5 to -15 kcal/mole.

Front 10

What are the 3 main lessons of protein folding?

Back 10

1. Evolution favors flexibility

2. Native proteins are on the borderline of denaturation

3. Misfolding is common.

Front 11

What are the 3 main functions of molecular chaperones?

Back 11

1. Protect new proteins from interference from other proteins

2. To accelerate slow steps

3. To ensure correct folding.

Front 12

Chaperone proteins are typically classified as what? And what does that mean?

Back 12

"Heat-shock proteins"

Their levels go up under stress and their function increases.

Front 13

What is a prime example of a heat shock protein? And what is it's mammalian equivalent?

Back 13

GroES-GroEL of bacteria.

TRiC is the mammalian equivalent.

Front 14

Besides GroEL-GroES, what is the other common heat shock protein and what does it do?

Back 14

Hsp 70; it assists folding the hydrophobic portion by binding to and protecting them.

Front 15

True/False: There is no energy required for the GroEL-GroEs complex.

Back 15

False. Energy is required to take on and off the cap.

Front 16

What is the purpose of PDI? and what does it stand for?

Back 16

PDI: protein disulphide isomerase. It breaks disulfide bonds, allowing incorrect ones to hopefully reform correctly.

Front 17

What does PPI stand for and what does it do?

Back 17

PPI: Peptidyl prolyl isomerase. It catalyzes cis-trans isomerization of X-P bonds. It changes the angle of proline bonds.

Front 18

Summarize the folding funnel

Back 18

As proteins fold, they move from a high energy state at the top of the funnel, to the lowest free energy state as the correctly folded protein. There are multiple pathways down.

Front 19

Name two diseases caused by improperly folded/made proteins.

Back 19

Alzheimer's disease

Creutzfeldt-Jacob disease (mad cow)

Cystic Fibrosis.

Front 20

Briefly describe Alzheimer's disease.

Back 20

During the formation of the amyloid protein, portions of the precursor protein must be chopped. If the wrong sections are cleaved first, the resulting pieces will join together and form a plaque that causes Alzheimer's.

Front 21

Briefly describe prion diseases

Back 21

a prion in its natural alpha helix dominant state will occasionally denature and reform into a beta sheet conformation spontaneously. If this improper conformation is not dealt with, it will affect more of the properly folded prions to become misfolded.