Lecture 5 - Elements of protein structure

Question 1

Peptide bond features

Answer 1

In proteins and peptides, amino acids are joined together by peptide bonds
Peptide bond is planar, trans and has a dipole

Question 2

Each protein is made up of at least one….

Answer 2

Protein (or polypeptide) chain

The amino acid residues in a polypeptide chain are numbered starting from the amino terminus to the carboxy terminus
Proteins may have anywhere from one to several chains
Proteins with one chain are the most common variety

Question 3

Proteins are mostly globular therefore

Answer 3

The main chain has to double back and form a more compact shape
THis structure will turn out to be comprised of primarily alpha-helix, beta sheet and turns

Question 4

Levels of protein structure

Answer 4

There are 4 levels - primary, secondary, tertiary and quaternary

Question 5

Primary

Answer 5

Amino acid sequence of a protein

Question 6

Secondary

Answer 6

3D arrangment of a protein chain over a short stretch of adjacent amino acid residues
What the primary structure does with residues adjacent to it

Question 7

Tertiary

Answer 7

3D structure of a complete protein chain

Question 8

Quaternary

Answer 8

Interchain packing and structure for a protein that contains multiple protein chains
Not all proteins have multiple chains so not all proteins have quaternary structure
This is how the chains pack together

Question 9

Main chain atoms in a protein are…

Answer 9

N, C⍺, C’

Question 10

Phi ɸ

Answer 10

Chain/rotation angles between N and C⍺

Question 11

Psi Ѱ

Answer 11

Chain/rotation angles between C⍺ and C’

Question 12

Phi and psi

Answer 12

These angles take on values ranging from 0 to +/- 180 degrees

Question 13

Omega ⍵

Answer 13

The chain angle between C’ and N is called by the greek omega and is usually very close to either 180 degrees or 0 degrees (trans 180 or cis 0)

The rotation angle around the peptide bond is called omega - no free spinning around this bond because it has partial double bond character, usually around zero

Third main chain angle - angle of rotation around the peptide bond

Is trans

Question 14

Protein 3D structure can be generally described by….

Answer 14

The rotation angles found around the bonds of the residues of the protein chain

Question 15

Phi-Psi restrictions

Answer 15

Phi-psi angles have restrictions in their values because of steric hinderance due to collisions

Phi rotation can lead to O-O collision
Psi rotation can lead to NH-NH collisions

Steric hinderance between the hydrogen on the amide nitrogen and the carbonyl oxygen

Question 16

Peptide bonds are mostly trans…

Answer 16

For a trans peptide bond, the C⍺ atoms are found on opposite sides of the peptide bond. In a cis peptide bond, the C⍺ atoms are found on the same side of the peptide bond. Steric crowding is increased for cis peptide bonds, very little rotation is allowed for the peptide bond

Look at alpha carbon to know if cis or trans

Proline is cis but the rest are pretty much trans

Question 17

3D structure of a protein determines …

Answer 17

Function - side chains orientated by the 3D structure, side chains are what carries out the chemistry

Question 18

Two dominant secondary protein structures

Answer 18

⍺- helix

Β-strand or beta-sheet

Question 19

Alpha helix

Answer 19

Main chain spirals around like a spiral staircase

In helices, not the interaction between residues that are 4 apart in the protein sequence

Question 20

In an alpha helice, what atoms hydrogen bond? How far apart are the N and O atoms in angstroms?

Answer 20

O and the hydrogen on the N, 2.9

Question 21

Beta strand or beta sheet

Answer 21

Beta strand is a single strand and a bunch of strands form a beta sheet

Question 22

Alpha helix key properties

Answer 22

3.6 residues/turn; 5.4Å/turn 

d = 1.5Å/residue 

spiral is “right handed” 

side chains point out from the helix axis 

dipole (are additive so that hydrogens are always pointing down in the same direction, this is because the bottom is more positive and the top is more negative)

ɸ=~-57􏰀,ψ=~-47􏰀 

Some residues e.g. are “helix breakers” e.g., glycine (due to flexibility), proline (these examples don’t like it because its side chain binds back to the amino group

Question 23

Beta sheet/strand key properties

Answer 23

Involves adjacent peptide chains, called b-strands, that have an extended structure that allows for hydrogen bonding between chains 

Hydrogen-bonding occurs between adjacent chains 

The chains often form a b-sheet, ≥ two b-strands 

Typically 2 to 10 strands per sheet 

Average strand length contains ~ 6 amino acid residues 

Each strand may have up to 15 residues 

Two types of interaction in a b-sheet: Parallel (2 independent main chains that are side by side, chains point from N to C terminus) and antiparallel (opposite direction)

Parallel and Antiparallel interactions

Usually between 6 and 15 amino acids in a strand

Arrow points from N terminus to C terminus

Question 24

What are the key properties of a β-sheet?

1. what bonding occurs between adjacent peptide chains (β-strands)?
2. Are there parallel, antiparallel or both interactions?
3. Where do side chains point?

Answer 24

1. Hydrogen bonding occurs between adjacent peptide chains (β-strands)
2. There can be parallel or antiparallel interactions
3. Side chains point above and below the sheet

Question 25

What are the key properties of a β-sheet?

1. Chains often form a β-sheet with typically how many strands per sheet?
2. what stretch of residues usually forms a β- strand?

Answer 25

1. Chains often form a β-sheet with typically 2 to 10 strands per sheet
2. Any NP-P-NP-P stretch of residues usually forms a β- strand

Question 26

What is the strand length of a β-sheet?

ie. how many amino acid residues?

Answer 26

The strand length ~6 amino acid residues

Question 27

Hydrogen bonds in beta vs alpha

Answer 27

Beta has interchain hydrogen bonds and alpha has intrachain hydrogen bonds

Question 28

To find a main chain

Answer 28

Find a nitrogen and then the carbonyl carbon for one strand

Then find out the alpha carbon

Question 29

Beta sheets: Number of strands, normal number of amino acids, maximum number of amino acids, what type of twist, silk repeating sequence, what direction do side chains point?

Answer 29

2-10, 6, 15, right handed, GSGAGA, up and down

Question 30

Key properties of turns

Answer 30

hairpin like, involve usually 3 or 4 residues 

high Gly, Pro content 

important, almost 30% residues involved in turns 

hydrogen bond, across the turn is common 

more than 16 types, given Roman Numeral names 

Type I, Type II are common types

Question 31

Protein structural shorthand

Answer 31

Helices shown as spirals (or cylinders) 

Strands shown as arrows, pointing from N to C 

Turns and random coil*, shown as loops or rope- like stretches

Question 32

Advantages of protein structural shorthand

Answer 32

Easily visualize the main chain path of protein 

Identify elements of secondary structure 

Allows an appreciation of proteins as 3-D objects 

Allows comparison to other proteins

Question 33

What residues are “helix breakers”?

Answer 33

Glycine is too flexible to adopt a helical structure

Proline always forces a turn because of its cyclic structure

Question 34

Location of the peptide, phi and psi bonds?

Answer 34

Ca-C = psi
N-Ca = phi
C-N = peptide