Fundamentals of Protein Structure

August, 2006 Tokyo University of Science Tadashi Ando

Our life is maintained by molecular network systems Molecular network system in a cell (From ExPASy Biochemical Pathways; http://www.expasy.org/cgi-bin/show_thumbnails.pl?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.

Alcohol dehydrogenase oxidizes alcohols to aldehydes or ketones Transport: Some proteins transports various substances, such as oxygen, ions, and so on.

Information transfer: For example, hormones.

Haemoglobin carries oxygen Insulin controls the amount of sugar in the blood

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

Glycine (G) 20 Amino acids Alanine (A) Valine (V) Isoleucine (I) Leucine (L) Proline (P) Methionine (M) Phenylalanine (F) Tryptophan (W) Asparagine (N) Glutamine (Q) Serine (S) Threonine (T) Tyrosine (Y) Cysteine (C) Asparatic acid (D) Glutamic acid (E) Lysine (K) Arginine (R) Histidine (H) White: Hydrophobic, Green: Hydrophilic, Red: Acidic, Blue: Basic

Proteins are linear polymers of amino acids

R 1 R 2 NH 3

＋

C H COO

ー ＋

NH 3

＋

C H COO

ー ＋

H 2 O R 1 R 2 H 2 O R 3

A carboxylic acid condenses with an amino group with the release of a water

NH 3

＋

A C H F CO NH Peptide bond G N S T C H D CO NH Peptide bond K G S C H A CO

The amino acid sequence is called as primary structure

Amino acid sequence is encoded by DNA base sequence in a gene

DNA molecule

＝ ・ G C G C T T A A G C G C ・ ・ C G C G A A T T C G C G ・

DNA base sequence

Amino acid sequence is encoded by DNA base sequence in a gene

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

DNA

Gene is protein’s blueprint, genome is life’s blueprint

Protein Gene Genome Gene Gene Gene Gene Gene Gene Gene Gene Gene Gene Gene Gene Gene Gene Protein Protein Protein Protein Protein Protein Protein Protein Protein Protein Protein Protein Protein Protein

Gene is protein’s blueprint, genome is life’s blueprint

Glycolysis network Genome Gene Gene Gene Gene Gene Gene Gene Gene Gene Gene Gene Gene Gene Gene Protein Protein Protein Protein Protein Protein Protein Protein Protein Protein Protein Protein Protein Protein

In 2003, Human genome sequence was deciphered!

Genome is the complete set of genes of a living thing.

In 2003, the human genome sequencing was completed.

The human genome contains about 3 billion base pairs.

The number of genes is estimated to be between 20,000 to 25,000.

The difference between the genome of human and that of chimpanzee is only 1.23%!

3 billion base pair => 6 G letters & 1 letter => 1 byte The whole genome can be recorded in just 10 CD-ROMs!

Each Protein has a unique structure Amino acid sequence NLKTEWPELVGKSVEE AKKVILQDKPEAQIIVL PVGTIVTMEYRIDRVR LFVDKLDNIAEVPRVG Folding!

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

Three-dimensional structure of proteins Tertiary structure Quaternary structure

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 ）

Close relationship between protein structure and its function

Example of enzyme reaction enzyme substrates

A

enzyme Hormone receptor Antibody

B Matching the shape to A

enzyme

A Digestion of A!

Binding to A

Protein structure prediction has remained elusive over half a century “ Can we predict a protein structure from its amino acid sequence?

” Now, impossible!

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.