1. Fundamentals of Protein Structure
August, 2006
Tokyo University of Science Tadashi Ando

2. Proteins play key roles in a living system
Three examples of protein functions
Catalysis: Almost all chemical reactions in a living cell are catalyzed by protein enzymes.
Transport: Some proteins transports various substances, such as oxygen, ions etc.
Information transfer: For example, hormones.
Alcohol dehydrogenase oxidizes alcohols to aldehydes or ketones
Haemoglobin carries oxygen
Insulin controls the amount of sugar in the blood

3. Amino acid: Basic unit of protein
COO-
NH3+ C R H
Different side chains, R, determin the properties of 20 amino acids.
Amino group
Carboxylic acid group
An amino acid

4. 20 Amino Acids Nonpolar, hydrophobic Polar, uncharged Polar, charged

5. Proteins are linear polymers of amino acids
NH3＋ C
COOー ＋
NH3＋ C
COOー ＋ H H
A carboxylic acid condenses with an amino group with the release of a water
H2O
H2O R1 R2 R3
NH3＋ C CO NH C CO NH C CO H
Peptide bond H
Peptide bond H
The amino acid sequence is called as primary structure F T D A G S K A N G S

6. Amino acid sequence is encoded by DNA base sequence in a gene
DNA molecule
DNA base sequence ・ C G A T ＝

7. Amino acid sequence is encoded by DNA base sequence in a gene
Second letter T C A G
First letter
TTT
Phe
TCT
Ser
TAT
Tyr
TGT
Cys
Third letter
TTC
TCC
TAC
TGC
TTA
Leu
TCA
TAA
Stop
TGA
TTG
TCG
TAG
TGG
Trp
CTT
CCT
Pro
CAT
His
CGT
Arg
CTC
CCC
CAC
CGC
CTA
CCA
CAA
Gln
CGA
CTG
CCG
CAG
CGG
ATT
Ile
ACT
Thr
AAT
Asn
AGT
ATC
ACC
AAC
AGC
ATA
ACA
AAA
Lys
AGA
ATG
Met
ACG
AAG
AGG
GTT
Val
GCT
Ala
GAT
Asp
GGT
Gly
GTC
GCC
GAC
GGC
GTA
GCA
GAA
Glu
GGA
GTG
GCG
GAG
GGG

8. Basic structural units of proteins: Secondary structure
α-helix
β-sheet
Secondary structures, α-helix and β-sheet, have regular hydrogen-bonding patterns.

9. Hierarchical nature of protein structure
Primary structure (Amino acid sequence) ↓
Secondary structure （α-helix, β-sheet）
Tertiary structure （Three-dimensional structure formed by assembly of secondary structures）
Quaternary structure （Structure formed by more than one polypeptide chains）

10. Primary Structure Polypeptide chains  Amino Acids
Largest polypeptide chain approx has 5000AA but most have less than 2000AA
Arrangement of the 20 amino acids in the polypeptide is the amino acid sequence which composes the primary structure of the protein
National Genome Research Institute
genome.gov

11. Secondary Structure
Secondary structures refers to the helical nature of the proteins.
The secondary structure is derived from the primary structure by the formation of hydrogen bond interactions between amino acid residues fairly close to one another
Secondary structure is defined by the patterns of hydrogen bonds formed between amine hydrogen and carbonyl oxygen atoms contained in the backbone peptide bonds of the protein
This leads to the folding of polypeptide chain into a helix

12. Tertiary Protein Structure
Defines the three dimensional conformation of an entire peptide chain in space
Determined by the primary structure
Modular in nature

13. Aspects which determine tertiary structure
Covalent disulfide bonds from between closely aligned cysteine residues form the unique Amino Acid cystine.
Nearly all of the polar, hydrophilic R groups are located in the surface, where they may interact with water
The nonpolar, hydropobic R groups are usually located inside the molecule

14. Motifs and Domains
Motif – a small structural domain that can be recognized in a variety of proteins
Domain – Portion of a protein that has a tertiary structure of its own. In larger proteins each domain is connected to other domains by short flexible regions of polypeptide.

15. Protein Folding
Protein folding constitutes the process by which a poly-peptide chain reduces its free energy by taking a secondary, tertiary, and possibly a quaternary structure

16. Quaternary Structure Not all proteins have a quaternary structure
A composite of multiple poly-peptide chains is called an oligomer or multimeric
Hemoglobin is an example of a tetramer
Globular vs. Fibrous

17. Three-dimensional structure of proteins
Tertiary structure
Quaternary structure

18. Close relationship between protein structure and its function
Example of enzyme reaction
Hormone receptor
Antibody
substrates A
enzyme
enzyme B
Matching the shape to A
Digestion of A!
enzyme A
Binding to A

19. Functions of proteins 1. Enzyme catalysts:
Almost all chemical reactions in the biological system are catalysed by enzymes.
The enzymes exhibit enormous catalytic power. They increases reaction rates at least a million fold.
Several thousand enzymes have been identified in the biological systems.
The striking fact it that all the enzymes are proteins.

20. Functions of proteins 2. Transport:
Proteins transport ions and small molecules across the cells of organism.
Haemoglobin, a conjugated protein of blood, transports oxygen.
Myoglobin, a muscle protein, transports oxygen in the muscles.
Transferrin carries iron in the plasma of blood.
The lipoproteins of plasma carry lipids from the liver to other organs
The membrane proteins transport glucose, amino acids and other nutrients across the cell membrane

21. Functions of proteins 3. Storage: 4. Nutrients:
Certain proteins functions as a storage of molecules,
Ferritin, a protein stores iron in the liver
4. Nutrients:
Certain proteins functions as nutrients
The egg contains ovalbumin
The milk contains casein
Contraction and movement:
The contraction of muscle is brought about by two fibrous proteins called actin and myosin
The microtubules of flagella and cilia are built on tubulin protein

22. Functions of proteins 6. Mechanical support:
Many proteins serve as supporting filaments, cables or sheets to give biological structures, strength, support and protection.
Collagen, a fibrous protein is the major component of cartilage and leather.
Keratin, an insoluble protein, is the main component of hair, finger nails and feathers.
Fibroin is the major component of silk fibres and spider web.

23. Functions of proteins 7. Immune protection: 8. Blood clotting:
Proteins defends organisms against invasion by other organisms.
Invading bacteria, virus, etc.. elicit the production of antibodies by lymphocytes. Antibodies neutralises the foreign germs
Antibodies are proteins, immunoglobulins.
8. Blood clotting:
Bleeding is stopped by the formation of clot. Clotting is brought about by blood clotting proteins such as fibrinogen and thrombin

24. Functions of proteins 9. Transmission of nerve impulse:
Acetylcholine, a receptor protein, helps to transmit nerve impulse.
10. Hormonal action:
Many hormones are proteins. Eg. Insulin, growth hormone, parathyroid hormone etc..
Gene expression:
In a cell, all the genes are not functioning at a time. Only few genes are active and the other genes remain in an inactive condition. The inactivation of genes is brought by repressor protein.

25. Summary Proteins are key players in our living systems.
Proteins are polymers consisting of 20 kinds of amino acids.
Each protein folds into a unique three-dimensional structure defined by its amino acid sequence.
Protein structure has a hierarchical nature.
Protein structure is closely related to its function.
Protein structure prediction is a grand challenge of computational biology.