Three dimensional structure of proteins

Question 1

What are polypeptide bonds?

Answer 1

• covalent linkages between amino acids
• form by condensation reactions, loss of water molecule (eliminates alpha carboxyl and amino group)
• independent of the amino acids being joined

Question 2

Residues:

Answer 2

Context of them being a peptide or polypeptide (residue 1: first amino acid)

Question 3

Main chain:

Answer 3

Constant portions, everything except side chains
(side chains are variables)

Common pattern NCCNCC

Question 4

Partial double bond characteristics:

Answer 4

• Rotation around C-N peptide bond is restricted
• six atoms of the peptide group are rigid and planar
• creates cis-trans isomers

Question 5

Resident structures:

Answer 5

Double bond can be shared (partial double bond characteristics:
- Lose freedom of rotating
- rigid and planar
- limit flexibility

Question 6

Configuration of Peptide bonds:

Answer 6

• peptide bonds tend to be in the trans configuration
• oxygen of the carbonyl and hydrogen of the amide group are usually trans to each other

Question 7

Why isn’t the cis configuration favoured for Peptide bonds?

Answer 7

• the cis configuration is more likely to cause steric interference between side chains
• usually proline residues if cis

Question 7

What are the four levels of protein structure?

Answer 7

1. Primary Structure
2. Secondary Structure
3. Tertiary Structure
4. Quaternary Structure

Question 7

Steric exclusion

Answer 7

Two groups can’t occupy the same space at the same time

Question 8

Primary Structure

Answer 8

Linear sequence of amino acids (tells you identity of amino acids and order, not position)
- Start at the N (amino) terminus and end at C (carboxyl) terminus
-cannot predict three-dimensional structure

Question 9

Secondary Structure

Answer 9

localized patterns of folding in a polypeptide
- maintained by hydrogen bonds between main-chain amide and carbonyl groups
- include alpha helices and beta sheets
-maintain same overall characteristics

Question 10

What are the two rules of secondary structure?

Answer 10

• they must optimize hydrogen bonding potential of main-chain carbonyl and amide groups (anything that can form a hydrogen will form one)
• They must represent a favoured conformation of the polypeptide chain (has to be allowed folding pattern)

Question 11

Main chain hydrogen bonding groups (secondary structure):

Answer 11

• Each peptide bond has a hydrogen bond donor (amide) and acceptor (carbonyl) groups
• always going to have same number of acceptors and donors
• important for optimizing hydrogen bonds

Question 12

What are Phi and Psi bonds?

Answer 12

Alpha carbons in main-chain through single bonds that have complete freedom of rotation (can range from -180 to 180)

Phi: angle between the alpha carbon and nitrogen atom
Psi: angle between alpha carbon and carbon of carbonyl group

Question 13

Alpha helix wrapping conformation:

Answer 13

• wraps around axis in a right handed manner with 4 residues/turn

Question 14

Which way does the alpha helix point to?

Answer 14

• N terminal (amide) to c terminal (carbonyl)
• positive to negative

Question 15

What amino acids are usually not found in alpha helixes?

Answer 15

Proline: too rigid
Glycine: flexibility makes it wobbly
Side chains of Val, Thr, Ile: due to steric interference
Ser, Asp, Asn near main chain: ones with hydrogen bonding near main-chain
Charged residues: tend to be positioned to form favourable ion pairs (residues of opposite charge separated by 3-4 positions)

Question 16

Why do the N and C terminuses have charges?

Answer 16

Every peptide bond has a small electrical dipole (gives the helix a net dipole)
- The longer and the more you have in a line the more polar and stronger the dipole is
- want to neutralize ends

Question 17

How is the dipole of a helix stabilized?

Answer 17

Residues are put at each termini whose charge oppose the helix dipole
N terminus: negatively charged residues (Asp, Glu)
C terminus: positively charged residues (Lys, Arg, His)

Question 18

There are two different faces of a helix:

Answer 18

• hydrophobic (non-polar) side
• Hydrophilic (polar) side

Question 19

Beta sheets

Answer 19

• involves multiple beta strands arranged side by side
• often 4 or 5 strands
• fully extended polypeptide chains

Question 20

Three types of beta sheets:

Answer 20

Parallel: strands run in the same direction (more flexible)
Anti-Parallel: strands run in opposite direction (more stable and stronger)
Mixed: contain both parallel and antiparallel

Question 21

Amphipathic beta sheets

Answer 21

• side chains alternate above and below the polypeptide chain (alternate polar on one side and non-polar on the other)

Question 22

Tertiary structure:

Answer 22

• final folding pattern of a single polypeptide chain
• Native conformation: biologically active form
• amino acid sequence determines tertiary structure
• can be made up of a bunch of weak interactions but makes an overall stable protein

Question 23

How is energy involved in the tertiary structure?

Answer 23

• protein conformation with the lowest free energy (the most stable) is usually the one with the maximum number of weak interactions
• stability reflects difference in free energies of folded and unfolded (what you started with vs what you end up with; protein has to find the most stable structure)

Question 24

Folding of proteins (tertiary):

Answer 24

• can be imagined as funnel, going from large number of unstable conformations and collapses into stable folding (rapid)
• goes from a higher entropy (randomness) to a low energy state of great stability
• some spontaneously fold some need chaperones

Question 25

Chaperones

Answer 25

assist in the help of folding a protein

Question 26

Denaturization

Answer 26

disruption of native conformation with loss of biological activity (the unfolding of a protein)
- energy needed for process is often small
- all or nothing: either going to fold properly or unfold

Question 27

What are the 3 characteristics of denaturation?

Answer 27

• rapid
• cooperative process (once it starts to fall apart it all falls apart)
• reversible (spontaneously fold back into position; no energy required)

Question 28

Quaternary Structure

Answer 28

Multiple subunits, each is a separate polypeptide
- could be same polypeptides or different ones
- subunits associate through noncovalent interactions (most important force stabilizing protein)
- more complex biological function

Question 29

What are some biological advantages with quaternary structures?

Answer 29

• help stabilize subunits and prolong protein’s life
• Unique active sites at interfaces between proteins
• unique and dynamic combinations of structure/function through physiological changes in tertiary/quaternary structure (hemoglobin)

Question 30

What are the biological roles of proteins?

Answer 30

• enzymes
• storage and transport
• physical cell support and shape
• mechanical movement
• decoding cell information
• hormones and hormone receptors (insulin)
• many other (antibodies)

Question 31

Protein size

Answer 31

• difference in proteins depend on the length
• typically 100 to 1000 acids in length
• largest protein discovered is Titin