Week 2: 3D Structure of Proteins

Question 1

What are protein chains?

Answer 1

Linear polyamides

Question 2

What is the rotation of the backbone constrained by?

Answer 2

a) partial double bond nature of peptide bond (omega) b) steric clash for the psi and phi

Question 3

What is secondary structure maintained by?

Answer 3

Hydrogen bonding

Question 4

Where are polar vs. nonpolar residues found on protein?

Answer 4

Polar residues tend to be found on outside, nonpolar on inside.

Question 5

What is the orientation of side chains in alpha helix?

Answer 5

adiate away from axis and point downward

Question 6

What is the orientation of side chains in beta sheets?

Answer 6

Alternating up and down

Question 7

What bonds to polar residues form with water on surface?

Answer 7

can form hydrogen bonds with each other and with water, van der Waals interactions occur, charged residues can also interact favorably with water

Question 8

What interactions occur among nonpolar residues shielded from water?

Answer 8

van der Waals interactions occur among closely-packed atoms

Question 9

What are the amino acids with aliphatic side chains?

Answer 9

G, A, V, L, I

Question 10

What are the amino acids with polar uncharged side chains?

Answer 10

S, T, N, Q, C

Question 11

What are the 3 consequences of hydrogen bonding?

Answer 11

1. Gives water high melting and boiling point 2. Means water can H-bond to polar molecules dissolved in it 3. Can influence how nonpolar molecules interact with it.

Question 12

What is heat capacity?

Answer 12

energy that must be added to raise or lower temp of substance by 1C, Liquid water has large heat capacity - is a temperature buffer. Are 15% fewer hydrogen bonds in liquid water than in ice. Water has high viscosity and high surface tension

Question 13

What is hydration? Hydration shells?

Answer 13

Water is a great ion solvent. The interactions of negative ends of water dipoles with cations and positive ends with anions in aqueous solution cause ions to become hydrated - surrounded by shells of oriented water molecules - hydration shells.

Question 14

What is a clathrate? What is hydrophobic effect?

Answer 14

When hydrophobic molecules do dissolve, the water lattice forms ice-like clathrate structures - cages - about nonpolar molecules - decreases entropy which is unfavourable thermodynamically. Therefore, water molecules tend to aggregate - releasing some molecules from clathrates, increasing entropy of solvent - hydrophobic effect - important to protein folding.

Question 15

What are fibrous proteins? Name 3

Answer 15

distinguished from globular proteins by long extended structure. Tend to be composed of single secondary structure type and have repeat sequences of residues that gives them their repeat structures and use just a few types of residues. Most play structural rolls.

Keratin, fibroin, collagen

Question 16

What are the two forms of keratin?

Answer 16

Alpha and Beta

Question 17

What are alpha keratins? Describe their structure

Answer 17

major proteins of hair and fingernails + major fraction of animal skin - members of broad group of intermediate filament proteins - important structural roles in cells - predominantly alpha-helical in structure. Have long sequences - over 300 residues that are alpha helical. Pairs of them twist about one another in left-handed coiled-coil structure. In every 3rd or 4th amino acid has a nonpolar, hydrophobic side chain. There is a strip of contiguous hydrophobic surface area along one face of helix - makes a shallow spiral. To maximize contact between hydrophobic surfaces, the two alpha- keratin helices entwine. The alpha-keratin molecule has small globular region covalently attached to coiled-coil. In intermediate filaments, pairs of the coils associate into flexible fibrils. alpha-keratin is hardened in some tissues because of introduction of disulfide cross-links.

Question 18

What can cysteine form?

Answer 18

Disulfide bonds

Question 19

Describe beta-keratin

Answer 19

The beta-keratins contain much more beta-sheet structure. found mostly in birds and reptiles in feathers and scales.

Question 20

Describe fibroin

Answer 20

beta-sheet structure used in silkworm and spider fibroin (spin fibres). Silkworm fibroin has long regions of stacked antiparallel beta sheets with polypeptide chains parallel to fiber axis. The stacked sheets are held together by noncovalent interactions between side chains. (Gly, Ala, Ser) - small amino acids. This allows sheets to fit together and pack on top of each other - strong and inextensible fiber but are very flexible because bonding between sheets involves only van der Waals interactions. There are compact folded regions that periodically interrupt the beta segments.

Question 21

Describe collagen

Answer 21

Collagen - most abundant protein in vertebrates - material in bond, tendons and skin. Basic unit is tropocollagen molecule - triple helix of 3 polypeptide chains - each 1000 residues long. The individual chains are left-handed helices - 3.3 residues/turn,. Three of the chains wrap in right handed sense with hydrogen bonds extending between them. Every third residue must be glycine - any other would be too bulky. The conformation of left-handed collagen helix is favored by presence of proline or hydroxyproline in tropocollagen molecule. Sequence: Gly-Proline-Proline or hydroxyproline and alanine. Proline favors an extended structure because of limited conformational flexibility. -OH groups in hydroxyproline stabilize the fiber. Hydroxylation of lysine residues also occurs in collagen - serving to form attachment for polysaccharides. The enzymes that catalyze hydroxylation’s require vitamin C, L-ascorbic acid. Scurvy is due to weakening of collagen fibers because of failure to hydroxylate side chains.

Question 22

What can proline not do? What does it favor?

Answer 22

Cannot make backbone peptide bonding. Cannot form alpha helixes or beta sheets. Favors extended rather than compact helixes

Question 23

How do tropocollagen molecules pack in collagen?

Answer 23

Individual tropocollagen molecules pack in collagen fibre in specific way. Each molecules is 300 nm long and overlaps neighbor by 640 amperes. Part of collagens toughness is due to cross-linking of tropocollagen molecules to each other via reaction involving lysine - some are oxidized to aldehyde derivatives (allysine) which can react with a lysine residue or with another one. The accumulating cross-links throughout life make collagen less elastic and more brittle.

Question 24

What are the common residues of keratin?

Answer 24

S, C, Q, E

Question 25

What is a beta-turn

Answer 25

Several varieties, each able to accomplish complete reversal of polypeptide chain direction in 4 residues - each case the carbonyl of residue i hydrogen-bonds to amine hydrogen of residue i + 3. Residues 1 and 4 are stabilized by a backbone H-bond.

Question 26

What is a type 1 beta turn?

Answer 26

Type 1 have Cis-Peptide bond between residues 2 and 3. The only residue at position 3 that favors this is proline. The cis-geometry permits the desired U-turn in chain direction for Type 1 turn

Question 27

What is a type II beta turn?

Answer 27

Type II beta turns have trans-geometry in central peptide bond between 2 and 3 - to avoid steric clash, residue at position 3 must be small - typically glycine.

Question 28

What does acetic acid form when it loses a proton?

Answer 28

Acetate - resonance stabilized/

Question 29

What is pKa? What does a lower pKa mean?

Answer 29

pKa - position of equilibrium - pH value - property of acid/conjugate base pair - pH at which [acid]/[conjugate base] = 1. The lower the pKa, the more the system favors deprotonation of acid. Above the pKa, deprotonated state is more common, below, the protonated state is more common, and at the pKa both states are equal.

Question 30

What are the negatively charged polar amino acids?

Answer 30

Aspartic acid and glutamic acid. - equilibrium lies toward deprotonated state at pH 7

Question 31

What are the positively charged polar amino acids?

Answer 31

Lysine, Arginine, Histidine.

Lysine and arginine both prefer protonated state at pH 7. Histidine has both protonated and deprotonated states at pH 7 (has basic imidazole ring)

Question 32

What are the aromatic residues?

Answer 32

F, Y, W - absorb light in UV-region of 250-350nm

Question 33

Describe methionine

Answer 33

Sulfur containing nonpolar residue (thioether) - nonpolar aliphatic. First residue to be translated in protein chain.

Question 34

Where are aromatic residues and methionine often found?

Answer 34

nonpolar core of globular proteins.

Question 35

Describe charge state of protein and isoelectric point.

Answer 35

Varies with pH - result of acidic and basic side chains

Isoelectric point - pH is equal to pI - overall charge is 0. At higher pH than pI - proteins will be more negative, at lower, more positive.