Introduction to Protein Structure

1. 1
Proteins
Structural Profiles and Properties
Abhijeet Kadam
TSEC
BioTechnology

2. 2
What do we Know about proteins ?
● Macromolecules
● Made up of 20 AA (residues)
● Certain no. Of AA required to perform a bio-function
● Min 40-50 AA in a useful protein
● 1000s of atoms arranged in 3D str. Unique for each
type
● It folds to make a 3D str.
● Shape decides the function
● Coded by a specific gene in DNA
● No mRNA – NO protein

3. 3
Amino Acids
● 20
● CO-R-N (R is a AA)
● Calpha – 4 ligands
● Chiral

4. 4
Types of AA
● Aliphatic – non polar R grp (glycine, alanine,
valine, leucine, isoleucine)
● Hydroxyl – polar R grp (serine, cysteine,
threomine, metheonine)
● Aromatic (trypsine, tryptophan, phenylalanine)
● Basic – +ve R grp (histidine, lysine, arginine)
● Acidic – -ve R grp ( aspartic acid, aspargine,
glutamin acid, glutamine)
● Cyclic – complicated – (proline)

5. 5
Protein Structure
● Function = structure
● Pri, sec, ter, quat.
● Primary – AA sequence
● Secondary – spatial arrangement of AA backbone
● Tertiary – 3D
● Quaternary – 3D of two or more proteins together
(subunits)

6. 6
Peptide Bond
● AA1 <------------------->AA2
Peptide bond
● A-carboxyl grp ---- a-amino grp
● A chain always has
– 1 free N terminal
– 1 free C terminal

7. 7
Poly peptide chain
● 2 AA combined in a condensation reaction
● Electrons get displaced to form peptide bonds
● Seq of AA --> pri str
● Counting starts from NH2 terminal
● Peptide bond angle – w – 180
● Phi and psi – variations
● But range of variation is fixed
● This gives sec str.
● These angles are represented by ramchandran plot

8. 8
Secondary structure elements
● No random coiling – fixed and accurate
● Hence the specific function of protein
● A small change – cause diseases (huntingtons – random
coiling)
● Most common str – a-helix & b-sheet
● Loops and turns of a&b – ter str.
● a&b form H-bonds and w/phi/psi angles
● b – parallel and antiparallel strands
● Hydrophobic side chains – interior
● Hydrophilic side chains – surface

9. 9
Secondary structure elements
● C=O and N-H are Polar
● If placed in hydrophobic – big problem
● But this is the central dogma
● Problem solved by H-bonds between amide protons and carbonyl
hydrogen
● Hence we get a-helix & b-sheet
● a-helix – protein twists
– R-grp facing outside from axis
– Stability provided with lots of H-bonds
● b-sheet – peptides run side by side
– H-bonds hold then together

10. 10
Loops and Turns
● Loops – connect a&b
– Irregular length and shape
– On surface
– No H-bonds with each other
– Form H-bonds with water
● Loops that join antiparallel b-sheets – turns
(hairpin loops)
– Loops of 2 types – I and II
– Depends on phi and psi of central residue

11. 11
Motifs
● Recurring elements
● Same motifs in many molecules but will always
be the dominant theme or the central theme
● 100,000 proteins – very few motifs

12. 12
Tertiary structure
● Proteins are globular or spherical
● Have many helices sheets non regular regions
● All these are folded in a specific manner

13. 13
Domains
● Chains >200 AA ----domains
● 3 types – a, b & a/b(made of b-a-b motifs)
● All proteins have a defined outside and inside
● Almost all hydrophobic – inside
● Almost all hydrophilic – outside
● Hence interaction with water is possible

14. 14
Quarternary structure
● More than one polypeptide chain held together
with different type of forces
● Forces like
– Van der waal
– London dispersion forces
– Salt bridges
– H-bonds

15. 15
Folding of protein
● A chain of AA has all the info to fold into a correct,
Active and 3D protein
● Steps are –
– Formation of sec str elements (nucleation foci)
– a-helix – most nucleation foci as it has AA near to each other
– Nuclei interact with each AA to form Domain
– Domains come together to form distorted ter str called molten
globe str
– Small rearrangements in distortion – 3D protein
– Any misfolds – huntingtons, cystic fibrosis, scurvy,
alzheimers etc

16. 16
●
Proteins
●
What do we Know about proteins ?
● Amino Acids
● Types of AA
●
Protein Structure
● Peptide Bond
●
Poly peptide chain
● Secondary structure elements
● Secondary structure elements
●
Loops and Turns
● Motifs
● Tertiary structure
●
Domains
●
Quarternary structure
●
Folding of protein