1. Hierarchy of Protein Structure
20 different amino acids: many combinations
The order of amino acids: Protein sequence
Primary Structure
Conformation varies depending on sequence
Secondary Structure
Overall structure of the chain in full 3D
Tertiary Structure

2. A protein of n residues 20n possible sequences!
Protein Sequences N C 1 2 3 4
Amino terminus
Carboxyl terminus
Residue number
20 different amino acids: many combinations
A protein of n residues 20n possible sequences!
100 residue protein has possibilities 1.3 X 10130!
The latest estimates indicate on 40,000 sequences in the human genome -> THERE MUST BE RULES!

3. *Length is generally 100-1000 residues*
Protein Sequences
*Length is generally residues*
Minimum length for performing a function ~40
Molecular machines not perfect- errors
Function requires specific amino acid properties
Not all amino acids are equally useful
Abundant: Leu, Ala, Gly, Ser, Val, Glu
Rare: Trp, Cys, Met, His
Post-translational modifications
Addition of co-factors- metals, hemes
Chemical modification- phosphate, glycos.

4. *Pattern is more important than exact sequence*
Protein Sequences
The pattern of amino acid side chains determines the secondary (and tertiary!!) structure
*Pattern is more important than exact sequence*
A T V R L L E W E D L
Reporting/Comparing Protein Sequences
A T V R L L E Y K D L 5 10
h-CaM
b-CaM
conservative
non-conservative

5. Secondary Structure Local structure of consecutive amino acids
Common regular secondary structures
a Helix
b Sheet
b turn
Amino acids have a greater propensity to form some secondary structures versus others
Chemical properties
Spatial constraints

6. The Peptide Bond Peptide plane is flat w angle ~180º
Partial double-bond:
-C - N- O = - H
-C = N- O-
Resonance structures

7. Backbone ConformationCa H R f 
Peptide planes
w angle is fixed, f and  angles vary
Many f/ combinations cause atoms to collide

8. Backbone ConformationCa H R f 
Side chains collision also limit f/ combinations
Backbone restricted  Secondary structure limited

9. Specific Secondary Structures
Three acceptable backbone f/ combinations
1. Right-hand helix: a-helix (-40°, -60°)
2. Extended: antiparallel b-sheet (140°, -140°)
3. Left-hand helix (rare): a-helix (45°, 45°)
Glycine: special because it has no side chain!
Side chains positioned to minimize collisions  amino acids prefer specific secondary structures
Hydrogen bonds between backbone atoms provide unique stability to secondary structures

10. Secondary Structure- b Sheet
Oxygen
Nitrogen
Hydrogen
Carbonyl C
Carbon a
R Group
H Bond

11. Secondary Structure- a Helix
H-bond

12. Secondary Structure- b Turn1 4 3 2
Reverses direction of the chain