Protein Structure

Insulin

Infinite variety The number of possible sequences is infinite An average protein has 300 amino acids, At each position there could be one of 20 different amino acids = possible combinations Most are useless Natural selection picks out the best table.htmlhttp:// table.html © 2007 Paul Billiet ODWSODWS

Proteins have four levels of organization

Formation of a Protein Protein Polypeptide

Primary structure is the amino acid sequence The numbers of amino acids vary (e.g. insulin 51, lysozyme 129, haemoglobin 574, gamma globulin 1250) The amino acid sequence determines how the polypeptide will fold into its 3D shape

Proteins have four levels of organization

Secondary Structure Regular, repeating 3D structures found in all polypeptide chains Secondary structure results from hydrogen bonding between the oxygen of one amino acid and the hydrogen of another. No R groups are involved! This produces the alpha helix and beta pleating The length of the helix or pleat is determined by certain amino acids that will not participate in these structures (e.g. proline)

The beta pleated sheet is formed by hydrogen bonds between parallel parts of the protein

The alpha helix is a coiled secondary structure due to a hydrogen bond every fourth amino acid

A single polypeptide may have portions with both types of secondary structure

Proteins have four levels of organization

TERTIARY STRUCTURE The folding of the polypeptide into areas whose chemical properties are determined by the R groups on the amino acids in the chain. MIL1 protein © Anne-Marie Ternes © 2007 Paul Billiet ODWSODWS

© Max Planck Institute for Molecular Genetics Chain B of Protein Kinase C

TERTIARY STRUCTURE Hydrophobic amino acids tend to arrange themselves inside the molecule Hydrophilic amino acids arrange themselves on the outside This folding is sometimes held together by strong covalent bonds (e.g. cysteine-cysteine disulphide bridge) Bending of the chain takes place at certain amino acids (e.g. proline) © 2007 Paul Billiet ODWSODWS

Tertiary structure depends on the interactions among the R group side chains

Types of interactions Hydrophobic interactions: amino acids with nonpolar side chains cluster in the core of the protein, out of contact with water = charged = hydrophobic

Types of interactions Hydrogen bonds between polar R groups

Types of interactions Ionic bonds between positively and negatively charged R groups

Types of interactions Disulfide bridge (strong covalent bonds) between sulfur atoms in the amino acid cysteine

Proteins have four levels of organization

Quaternary structure results from interactions among separate polypeptide chains.

QUATERNARY STRUCTURE Some proteins, not all, are made of several polypeptide subunits (e.g. haemoglobin has four) Protein Kinase C © Max Planck Institute for Molecular Genetics © Text 2007 Paul Billiet ODWSODWS

QUATERNARY STRUCTURE These subunits fit together to form the functional protein Therefore, the sequence of the amino acids in the primary structure will influence the protein's structure at the second, third and fourth levels. © 2007 Paul Billiet ODWSODWS

For example, hemoglobin is composed of 4 polypeptide chains

Even a slight change in the amino acid sequence can cause the protein to malfunction For example, mis-formed hemoglobin causes sickle cell disease

Extras /animations/protein_folding/protein_f olding.htmhttp:// /animations/protein_folding/protein_f olding.htm proteins.htmlhttps://mywebspace.wisc.edu/jonovic/web/ proteins.html hive/animations/hires/a_proteo1_h.htmlhttp:// hive/animations/hires/a_proteo1_h.html