1. Protein backbone Biochemical view:
basic repeating unit is NH—CαH—C’=O
We can also look at repeating units from Cα to Cα
Interesting properties:
Bond lengths almost equal in all groups, in all proteins
Bond angles almost equal in all groups, in all proteins
A Cα atom belongs to two units
All atoms in an unit coplanar
Preferable when describing structural properties

2. Protein backbone
Geometric/Structural view: polypeptide chain divided into
Peptide units
Cα atom and carboxyl group of residue i
Amino group and Cα atom of residue i+1
Are rigid groups
Rotation on bond C-N is prevented by energy barrier
Peptide units are joined by covalent bonds between Cα atoms. Thus
Peptides can rotate along 2 bonds:
N-Cα and Cα-C
Two dihedral angles for each unit: Ф (Phi) and Ψ (Psi)
Two degrees of freedom per unit
Determine the conformation of the backbone

3. Dihedral angles and regular structures
Repeating values of Ф and Ψ along the main chain result in regular structure
repeating values of Ф =-57o and Ψ =-47o give a right-handed helical fold (α-helix)
repetitive values of Ф[-110,-140] and Ψ[+110,+135] give sub chains with conformations that allow interactions between nearby parallel segments (β-sheet)
Most combinations of Ф and Ψ angles are not allowed
Allowed conformations plotted as 2-D chart
Ramachandran plot

4. Secondary Structure
defined by patterns of hydrogen bonds between backbone amide groups
sidechain-mainchain and sidechain-sidechain hydrogen bonds are irrelevant
The amino acids in the interior/core of a globular protein have hydrophobic side chains
Water soluble proteins fold to pack hydrophobic side chain into interior
Results in hydrophobic core and hydrophilic surface
The main chain must fold into interior, too
Main chain is hydrophilic:
N--H: hydrogen bond donor
C=O: hydrogen bond acceptor
These groups must be neutralized by formation of H bonds  secondary structure
Secondary structure
α-helices
β-sheets
form rigid and stable frameworks

5. α-Helix Righthanded coiled conformation Has between 4 to 40 residues
backbone N-H group i+4 forms hydrogen bonding with backbone C = O group i
3.6 residues per turn (5.4 Å, 1.5 Å per residue)
Variations, with chain more loosely or tightly coiled are possible (i+3 or i+5 instead of i+4) but not often
backbone (φ, ψ) dihedral angles around (-60o,-45o)
Sum of φ and ψ angles of consecutive residues about 105o
Has between 4 to 40 residues
All H bonds point in the same direction
Aligned along helical axis
Dipole moments for residues are aligned along axis
Net dipole for α-helix (+ at N-H end and – at C=O end)

6. Representations (cartoon, backbone trace, space filling)

7. β-sheets
Combination of several regions of the chain (not chain adjacent): β-strands
Parallel: all amino acids go in same direction
Evenly spaced H bonds
Antiparallel: amino acids in successive strands alternate directions
Alternate narrowly/widely spaced H bonds
Mixed β-sheet also exist
Have twisted strands: right-handed twist (always)
β-strand: 5 to 10 residues long
Almost fully extended

8. Representations (bond, cartoon, ribbon)

9. From secondary structure to structure
Protein structure: built from secondary structures
Connected by loop regions
Various lengths
Irregular shape
Are at the surface of the protein
Reach in charged and polar residues
Easier to predict!
In homologous proteins almost always insertions and deletions occur in the loop regions.

10. Structure Motifs Secondary structures  connected to form motifs
α-helices and β-sheets in a motif
Adjacent in the 3-dimensional structure
Connected bu loop regions
Combinations of motifs and secondary structures  domains

11. Native conformation: direct consequence of
Tertiary structure:
Arrangement of secondary structure
Structural domains
Quaternary structure
More than one polypeptide folded together
Native conformation: direct consequence of
primary structure
chemical environment
water based
oily interior of a cell membrane
So far, no reliable computational method exists to predict the native structure from the amino acid sequence

12. Structure Classes Protein structure  four classes: α-domains
core built up only from α-helices
β-domains
core built up only from (usually 2) antiparallel β-sheets
α/β-domains
mostly β-α-β motifs
(mostly) parallel β-sheets surrounded by α-helices
α+β-domains (few cases)
antiparallel β-sheet packed against α-helices