Primary & Secondary Structure

Question 1

Describe the primary structure of a protein

Answer 1

• Linear sequence of amino acids (30-1000+)
• Unique sequence for a protein
• Sequences can be compared against a database to reveal relationships

Question 2

Peptide bonds

Answer 2

Condensation of alpha carbon of one amino acid with the alpha carbon of another gives rise to a peptide bond

Formation of the peptide bond eliminates the ionisable alpha carboxyl and alpha amino groups of the free amino acids

Question 3

Polypeptide chain nomenclature

Answer 3

• amino acid residues compose peptide chains
• peptide chains are numbered from the N (amino) terminus to the C (carboxyl) terminus
• the repeating N-C alpha-C unit constitutes the backbone of the peptide chain

Question 4

What is the space filling model?

Answer 4

A representation of protein structure

Shows overall shape of the protein but can’t see anything specific

Question 5

3D structure and function

Answer 5

• Protein conformation = 3D shape
• Native conformation = polypeptide chain folds into a single stable shape, determined by sequence of amino acids
• Biological function of a protein depends completely on its native conformation

Question 6

2 key factors for protein structure

Answer 6

1. Allowable bond rotations around the backbone define the possible conformations of the polypeptide chain
2. Weak noncovalent interactions between the backbone and side chain groups

Question 7

Planar peptide groups

Answer 7

The C-N peptide bond has double bond character (due to resonance) resulting in:
- no bond rotation around C-N but can still flip from one orientation to another
- 6 atoms all lying in the same plane = peptide group

Question 8

Cis and Trans conformations

Answer 8

• double bond character means distinct cis and trans conformations are possible around the C-N linkage
• Cis conformation is less favourable than trans due to steric interference of alpha carbon side chains
• nearly all peptide groups in proteins are in the trans conformation

Question 9

Rotation of bonds in a peptide group

Answer 9

• each amino acid in a polypeptide contributes 3 atoms (N-C∂-C) to the backbone
• rotation is possible
• but is restricted to allowable bond angles by steric interference between main chain and side chain atoms
• in proline, rotation of the N-C∂ is restricted due to its ring structure

Question 10

Key features of the secondary structure

Answer 10

• alpha helix
• beta strands and sheets
• favoured by allowable bonds and stabilising hydrogen bonds

Question 11

Structure of an alpha helix

Answer 11

Right-handed because all amino acids are L-amino acids

Backbone turns clockwise, viewed from N terminus

Question 12

Features of alpha helix

Answer 12

• each C=O (residue n) forms a hydrogen bond with the amide hydrogen of residue n+4
• stabilised by many hydrogen bonds which are parallel to the long axis of the helix
• all C=O groups point towards the C terminus
• all side chains point outwards

Question 13

Key properties about Alpha helix structure

Answer 13

Pitch = advance along the helix long axis per turn = 0.54 nm

Rise = each residue advances by 0.15 nm along the long axis of the helix

3.6 amino acids per turn

Rise x Number of amino acids = pitch

Question 14

How can alpha helices be amphipathic?

Answer 14

Hydrophobic resides are directed inwards and hydrophilic residues are directed outwards

Question 15

What are ß strands?

Answer 15

Polypeptide chais that are almost fully extended

Cannot exist on their own = not stable individually

Question 16

What are ß sheets?

Answer 16

Multiple ß strands arranged side by side

Stabilised by hydrogen bonds between C=O and NH on adjacent strands

Question 17

Parallel vs antiparallel ß sheets

Answer 17

Parallel = stands run in the SAME N to C terminal direction

Antiparallel = strands run in OPPOSITE N to C terminal directions

Question 18

What are ßsheets separated by?

Answer 18

Alpha helices

Question 19

Properties of parallel and antiparallel ß sheets

Answer 19

Form hydrogen bonds between 2 adjacent strands that are side to side

Neatly aligned = antiparallel
Zig-zag = parallel

Parallel ß sheets are slightly less stable than antiparallel ones

Question 20

Interactions of ß sheets

Answer 20

• ß strand side chains project alternatively above and below the plane of the ß sheet
• ß sheets are pleated
• R groups (side chains) are on alternating surfaces
• Side chains on adjacent strands are usually in adjacent positions (on the same face)
• Nature of side chains can influence interactions of a ß sheet with other parts of a protein structure

Question 21

What are loops and turns?

Answer 21

Loops and turns connect alpha helices and ß strands and allow a peptide chain to fold back on itself to make a compact structure

Loops = often contain hydrophilic residues and are found on protein surfaces

Turns = loops containing 5 residues or less, connect ß strands