Lecture 2

Question 1

random coil

Answer 1

parts of polypeptide chain that don’t have discernible repeating pattern (ie alpha helix/beta sheets)
- structure determined by amino acid sequence

Question 2

what are the two major types of tertiary structure?

Answer 2

globular and fibrous

Question 3

globular tertiary structure

Answer 3

polypeptide folds into complex compact of shape like a ball
- water soluble
(ie enzymes, hemoglobin)

Question 4

fibrous tertiary structure

Answer 4

simple, elongated 3D structure
- play role in cells that need molecules to travel far
(ie extracellular matrix protein: collagen, a-keratin)

Question 5

subunit (quaternary structure)

Answer 5

polypeptide chain that makes up quaternary structure
- structure can be identical or different (dimer, trimer, tetramer, oligomer)

Question 6

how are quaternary structure subunits hold together?

Answer 6

noncovalent forces

Question 7

what exhibits allosteric properties?

Answer 7

multisubunit proteins
- subtle structure changes in one part of protein causing changes in function of another part

Question 8

what can induce protein denaturation?

Answer 8

heat, high/low pH, detergents, urea and guanidine hydrochloride

Question 9

what facilitates protein denaturation?

Answer 9

• reducing agents —> they reduce disulfide bonds
• urea improves accessibility of reducing agents to internal disulfide bonds

Question 10

what are the consequences of protein denaturation?

Answer 10

• decreased protein solubility = hydrophobic groups can lead to aggregation and precipitation
• increased/decreased susceptibility to hydrolysis by proteolytic enzymes
• total loss of biological activity

Question 11

what is the anfinsen experiment?

Answer 11

determined all information necessary to determine the tertiary structure of a protein is provided by its amino acid sequence

Question 12

molecular chaperones (chaperonins)

Answer 12

proteins that assist in living cells for protein folding

Question 13

heat-shock proteins

Answer 13

major class of chaperonins, that are synthesized in response to heat shock or other stresses

Question 14

does chaperones require energy?

Answer 14

yes, they bind in ways that are most energetically favored

Question 15

why are chaperones used in the protein folding process?

Answer 15

b/c they make the folding process more reliable (even if shape is based on primary sequence)

Question 16

what other factors facilitate protein folding?

Answer 16

ionic environment, enzymes (protein disulfide isomerase), cofactors (metal ions, organic compounds)

Question 17

example of conformational disease

Answer 17

marfan’s syndrome

Question 18

what characteristics does conformational diseases have?

Answer 18

-does not function or assemble
- “toxic folds” that trigger harmful protein aggregates
- defects in cellular trafficking

Question 19

what gene mutation causes marfan syndrome?

Answer 19

fibrillin –> elastin to elastic fibers

Question 20

what causes conformational diseases?

Answer 20

• change in amino acid sequence
• defect in parents
• nutrition deficiencies (vit C –> scurvy)

Question 21

amyloid

Answer 21

deposits of protein aggregates that happen in and around cells

Question 21

common properties of aggregating proteins

Answer 21

• rich in b-sheets
• transformation of helical structure to b-sheet

Question 22

amyloidosis

Answer 22

accumulation of amyloid deposits –> alzheimer’s disease, prion disease

Question 23

prion proteins are responsible for what type of disease?

Answer 23

neurodegenerative disease

Question 24

examples of neurodegenerative diseases that are caused by prions

Answer 24

• CJD (humans)
• mad cow disease
• scrapie (sheep)

Question 25

where are prions found?

Answer 25

outer surface of plasma membrane (most abundant in neurons)

Question 26

normal prion is in what form? what about mutated form?

Answer 26

normal = a helix
abnormal = b sheet, aggregates and protease resistant

Question 27

who discovered prions?

Answer 27

stanley B. prusiner

Question 28

what causes fetal familial insomnia (FFI)?

Answer 28

genetic mutation taht results in substitution of asparagine for aspartic acid in PrPc
- affects the thalamus

Question 29

what is the most common cause of blindness?

Answer 29

cataracts –> aggregation of partially unfolded lens proteins

Question 30

crystallin proteins

Answer 30

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

Question 31

what is the most abundant protein in mammals?

Answer 31

collagen –> 25% of total protein mass in mammals

Question 32

what is collagen?

Answer 32

fibrous protein that forms very stiff and strong cables
- secreted by connective tissue cells

Question 33

what is the structure of collagen molecules?

Answer 33

tropocollagen: 3 polypeptide chains wrapped forming superhelix

Question 34

what is the amino acid composition of collagen?

Answer 34

1/3 –> glycine
rich in proline
hydroxyproline and hydroxylysine

Question 35

what is the purpose of proline in collagen?

Answer 35

• 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

Question 36

what is the purpose of glycine in collagen?

Answer 36

smallest amino acid, only reside that can fit in middle of triple helix

Question 37

what vitamin is required to form hydroxylproline and hydroxylysine?

Answer 37

vitamin C –>reducing agent that maintains enzymes in active form, keeping iorn atoms in reduced ferrous state

Question 38

what disease is caused by vitamin c deficiency?

Answer 38

scurvy –> a chains are not hydroxylated failing to form triple helix

Question 39

collagen cross links

Answer 39

intramolecular and intermolecular covalent cross links form between modified lysine residues that further stabilize collagen fibril

Question 40

what is the major source of ATP in aerobic organisms?

Answer 40

oxidative phosphorylation

Question 41

what are the two major mechanisms for delivering oxygen?

Answer 41

circulatory system –> oxygen to cells
oxygen carrying proteins –> myoglobin and hemoglobin

Question 42

where is myoglobin found? what is its function?

Answer 42

• found in muscle
• reserve supply of oxygen, facilitates movement of oxygen within muscle

Question 43

function of hemoglobin

Answer 43

• increase oxygen transporting capacity of blood
• transport of CO2 and hydrogen ions in blood

Question 44

prosthetic groups

Answer 44

non protein components that are tightly bound to many proteins and contribute to their biological activities

Question 45

apoprotein

Answer 45

protein without prosthetic group