Lecture 2 Flashcards
random coil
parts of polypeptide chain that don’t have discernible repeating pattern (ie alpha helix/beta sheets)
- structure determined by amino acid sequence
what are the two major types of tertiary structure?
globular and fibrous
globular tertiary structure
polypeptide folds into complex compact of shape like a ball
- water soluble
(ie enzymes, hemoglobin)
fibrous tertiary structure
simple, elongated 3D structure
- play role in cells that need molecules to travel far
(ie extracellular matrix protein: collagen, a-keratin)
subunit (quaternary structure)
polypeptide chain that makes up quaternary structure
- structure can be identical or different (dimer, trimer, tetramer, oligomer)
how are quaternary structure subunits hold together?
noncovalent forces
what exhibits allosteric properties?
multisubunit proteins
- subtle structure changes in one part of protein causing changes in function of another part
what can induce protein denaturation?
heat, high/low pH, detergents, urea and guanidine hydrochloride
what facilitates protein denaturation?
- reducing agents —> they reduce disulfide bonds
- urea improves accessibility of reducing agents to internal disulfide bonds
what are the consequences of protein denaturation?
- decreased protein solubility = hydrophobic groups can lead to aggregation and precipitation
- increased/decreased susceptibility to hydrolysis by proteolytic enzymes
- total loss of biological activity
what is the anfinsen experiment?
determined all information necessary to determine the tertiary structure of a protein is provided by its amino acid sequence
molecular chaperones (chaperonins)
proteins that assist in living cells for protein folding
heat-shock proteins
major class of chaperonins, that are synthesized in response to heat shock or other stresses
does chaperones require energy?
yes, they bind in ways that are most energetically favored
why are chaperones used in the protein folding process?
b/c they make the folding process more reliable (even if shape is based on primary sequence)
what other factors facilitate protein folding?
ionic environment, enzymes (protein disulfide isomerase), cofactors (metal ions, organic compounds)
example of conformational disease
marfan’s syndrome
what characteristics does conformational diseases have?
-does not function or assemble
- “toxic folds” that trigger harmful protein aggregates
- defects in cellular trafficking
what gene mutation causes marfan syndrome?
fibrillin –> elastin to elastic fibers
what causes conformational diseases?
- change in amino acid sequence
- defect in parents
- nutrition deficiencies (vit C –> scurvy)
amyloid
deposits of protein aggregates that happen in and around cells
common properties of aggregating proteins
- rich in b-sheets
- transformation of helical structure to b-sheet
amyloidosis
accumulation of amyloid deposits –> alzheimer’s disease, prion disease
prion proteins are responsible for what type of disease?
neurodegenerative disease
examples of neurodegenerative diseases that are caused by prions
- CJD (humans)
- mad cow disease
- scrapie (sheep)
where are prions found?
outer surface of plasma membrane (most abundant in neurons)
normal prion is in what form? what about mutated form?
normal = a helix
abnormal = b sheet, aggregates and protease resistant
who discovered prions?
stanley B. prusiner
what causes fetal familial insomnia (FFI)?
genetic mutation taht results in substitution of asparagine for aspartic acid in PrPc
- affects the thalamus
what is the most common cause of blindness?
cataracts –> aggregation of partially unfolded lens proteins
crystallin proteins
structural and chaperone proteins in lens of eye
- reduction in chaperone function = leads to increases in denatured proteins
- alterations in a-crystallin oligomeric structure = leads to co-aggregation of a-crystallin and substrates
what is the most abundant protein in mammals?
collagen –> 25% of total protein mass in mammals
what is collagen?
fibrous protein that forms very stiff and strong cables
- secreted by connective tissue cells
what is the structure of collagen molecules?
tropocollagen: 3 polypeptide chains wrapped forming superhelix
what is the amino acid composition of collagen?
1/3 –> glycine
rich in proline
hydroxyproline and hydroxylysine
what is the purpose of proline in collagen?
- stabilizes helical conformation through steric repulsion of pyrrolidone rings on the outside of chains
- hydroxyl groups of hydroxyproline form interchain H bonds and H bonds with water, stabilizing the triple helix
what is the purpose of glycine in collagen?
smallest amino acid, only reside that can fit in middle of triple helix
what vitamin is required to form hydroxylproline and hydroxylysine?
vitamin C –>reducing agent that maintains enzymes in active form, keeping iorn atoms in reduced ferrous state
what disease is caused by vitamin c deficiency?
scurvy –> a chains are not hydroxylated failing to form triple helix
collagen cross links
intramolecular and intermolecular covalent cross links form between modified lysine residues that further stabilize collagen fibril
what is the major source of ATP in aerobic organisms?
oxidative phosphorylation
what are the two major mechanisms for delivering oxygen?
circulatory system –> oxygen to cells
oxygen carrying proteins –> myoglobin and hemoglobin
where is myoglobin found? what is its function?
- found in muscle
- reserve supply of oxygen, facilitates movement of oxygen within muscle
function of hemoglobin
- increase oxygen transporting capacity of blood
- transport of CO2 and hydrogen ions in blood
prosthetic groups
non protein components that are tightly bound to many proteins and contribute to their biological activities
apoprotein
protein without prosthetic group
