Protein Structure And Folding Flashcards
Why is shape of the protein so important?
Shape determines function
Not in correct shape– won’t function
Proteins need to interact with specie substrates/proteins
Denaturation
Extreme unfolding of a protein in which all secondary and tertiary is lost
Breaks hydrogen bonds but not covalent bonds between amino acids
Renaturation
Refolding if an unstructured protein into its tertiary structure
Anfinsen’s experiment
Chemical + amino acid= denaturation
Remove chemical and protein refolds
Side chain interactions in tertiary structure
Amino acids can be far away in sequence but close in 3D form
Amino acid movement
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
Levinthal’s paradox
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
Protein folding landscape
May not take the same oath but always end up same way
Misfold=can’t bind it the right molecule;lose function; toxic
Factors that disrupt protein folding
Heat Detergents Solvents pH Reducing agents
Reducing agents
Chemicals that can break disulfide bonds
Ex. Perm–chemically alters hair
Detergents
Molecules that can interact with both hydrophilic and hydrophobic compounds
Ex. Dish soap, stains
pH
Changes in the pH of a solution leads to disruption of hydrogen and ionic bonds within a protein
Ex. Breakdown of food in stomach
Solvent
Water (polar solvent)
Heat
Heat unfolds proteins, causing them to aggregate together
Ex. Eggs –denaturation
Protein aggregation
Many proteins binding (accumulating) together in very large complexes (clumps) Misfolded proteins Aggregation is uncontrolled Becomes insoluble Toxic to the cell
Amyloids
Highly organized, stable protein aggregates that form long, insoluble givers (fibrils)
Biofilm
Aggregate if microorganisms in which cells are stuck to each other and/or to a surface coated in this protective film
Quality control pathways
Regulate protein folding and aggregation
Destroy protein/refold
Proteasome
Molecular chaperones
Proteasome
Quality control pathway
Large complex that destroys specific proteins
Proteins need to be marked for removal (ubiquitan)
“Paper shredder”
Molecular chaperones
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
HSP60
Around all the time
Holds 6-7 seconds to refold
HSP70/40
True heat shock proteins
Binds to hydrophobic residues so they can’t bind with one another
HSP90
Binds to hydrophobic residues so they can’t bind with one another
HSP100
When things start to aggregate, it breaks apart large aggregates of proteins
Humans do NOT have HSP100
