Protein Structure And Folding

Question 0

Why is shape of the protein so important?

Answer 0

Shape determines function

Not in correct shape– won’t function
Proteins need to interact with specie substrates/proteins

Question 1

Denaturation

Answer 1

Extreme unfolding of a protein in which all secondary and tertiary is lost

Breaks hydrogen bonds but not covalent bonds between amino acids

Question 2

Renaturation

Answer 2

Refolding if an unstructured protein into its tertiary structure

Question 3

Anfinsen’s experiment

Answer 3

Chemical + amino acid= denaturation

Remove chemical and protein refolds

Question 4

Side chain interactions in tertiary structure

Answer 4

Amino acids can be far away in sequence but close in 3D form

Question 5

Amino acid movement

Answer 5

Side chains can move freely and make many different shapes/connections

Peptide bind locked into specific positions

Each amino acid in protein has many different positions that directly alter 3D shape of protein

Question 6

Levinthal’s paradox

Answer 6

How do proteins fold in milliseconds?– it would take too long for a protein to fold by random sampling

Protein folding = processive– certain structures lock into place, move to next structure

Question 7

Protein folding landscape

Answer 7

May not take the same oath but always end up same way

Misfold=can’t bind it the right molecule;lose function; toxic

Question 8

Factors that disrupt protein folding

Answer 8

Heat
Detergents
Solvents
pH
Reducing agents

Question 9

Reducing agents

Answer 9

Chemicals that can break disulfide bonds

Ex. Perm–chemically alters hair

Question 10

Detergents

Answer 10

Molecules that can interact with both hydrophilic and hydrophobic compounds

Ex. Dish soap, stains

Question 11

pH

Answer 11

Changes in the pH of a solution leads to disruption of hydrogen and ionic bonds within a protein

Ex. Breakdown of food in stomach

Question 12

Solvent

Answer 12

Water (polar solvent)

Question 13

Heat

Answer 13

Heat unfolds proteins, causing them to aggregate together

Ex. Eggs –denaturation

Question 14

Protein aggregation

Answer 14

Many proteins binding (accumulating) together in very large complexes (clumps)
Misfolded proteins
Aggregation is uncontrolled 
Becomes insoluble
Toxic to the cell

Question 15

Amyloids

Answer 15

Highly organized, stable protein aggregates that form long, insoluble givers (fibrils)

Question 16

Biofilm

Answer 16

Aggregate if microorganisms in which cells are stuck to each other and/or to a surface coated in this protective film

Question 17

Quality control pathways

Answer 17

Regulate protein folding and aggregation
Destroy protein/refold

Proteasome
Molecular chaperones

Question 18

Proteasome

Answer 18

Quality control pathway
Large complex that destroys specific proteins
Proteins need to be marked for removal (ubiquitan)

“Paper shredder”

Question 19

Molecular chaperones

Answer 19

Quality control pathway
Proteins that assist the non covalent folding/refolding of other proteins

Heat shock proteins (HSP)--made to survive until you get out of heat shock (high heat -> protein misfolding)
HSP60
HSP40/70
HSP90
HSP100

Question 20

HSP60

Answer 20

Around all the time

Holds 6-7 seconds to refold

Question 21

HSP70/40

Answer 21

True heat shock proteins

Binds to hydrophobic residues so they can’t bind with one another

Question 22

HSP90

Answer 22

Binds to hydrophobic residues so they can’t bind with one another

Question 23

HSP100

Answer 23

When things start to aggregate, it breaks apart large aggregates of proteins
Humans do NOT have HSP100