8/19 - Chapter 4: Proteins 3D Structure & Folding

Hydrophobic effect

release of water molecules from the structured layer around the molecule as protein folds increase entropy

Ionic bonds

bonds formed between oppositely charged ions

Hydrogen bonds

interaction of N-H and C=O of peptide bond leads to α-helices and β-sheets

Disulfide bonds

covalent bonds derived from 2 thiol groups, strongest contributing to protein structure formed by oxidation of thiol groups on cysteine

London dispersion

medium range weak attraction between all atoms contributes to stability

Electrostatic interactions

long-range strong interactions between permanently charged groups; e.g. salt bridges

α-helix

forms when CO group forms H-bond with NH group situated 4 residues ahead; all are right-handed

β-strand

side chains are alternately above and below the plane of the strand; rare because they are less stable but can line up to form β-sheets

Protein folding

process by which a protein structure assumes its functional shape or conformation

Hydrophobic collapse

hydrophobic resides spontaneously collapse into the interior of the molecule

How can energy confirmations affect folding?

Sometimes the most functional form is not the lowest confirmation, leading to misfolding

Improper degradation

cellular degradation systems can be overactive, degrading proteins with functionality; e.g. cystic fibrosis

Improper localization

mutations in folding can cause proteins to go to the wrong location; e.g. α1-antitrypsin leading to emphysema

Dominant-negative mutations

mutant form of protein is destructive; e.g. mutant keratin leading to blistering

Gain of toxic function

e.g. APOE4 stabilizes alternate conformation, changing lipid affinity, disrupting mitochondrial function and impairing neurite growth

Amyloid accumulation

layers of β-sheets forming plaques and leading to degenerative disease e.g. parkinson’s, huntington’s

Mad cow disease

misfolded prion protein contains more β-sheets than typical prion

Diabetic cataract

crystalline of eyes from amyloid fibers, causing clouded vision

Denaturation

misfolding due to disruptions of bonds

How does heat cause denaturation?

Affects weak interactions, H-bonds

How do acids and bases cause denaturation?

disrupts salt bridges

How do organic solvents (alcohol, acetone, diethyl ether) cause denaturation?

disrupts H-bonds between amide groups in secondary structure and side chains in tertiary structure

How do detergents cause denaturation?

amphipathic, pulling apart the hydrophilic and hydrophobic sides

How does lowered pH causes denaturation?

A lower pH protonates more functional groups

How do salts of heavy metals cause denaturation?

Salts are ionic in nature, disrupting salt bridges and making protein insoluble

Chaperones

Act in the rough ER and assist in correct protein folding