PROTEINS FOLDED POLYPEPTIDES

PRIMARY STRUCTURE The order and sequence of amino acids MIL1 protein sequence: >gi|7662506|ref|NP_056182.1| MIL1 protein [Homo sapiens] M/E/D/C/L/A/H/L/G/E/K/V/S/Q/E/LKEPLHKALQMLLSQPVTYQAFRECTLETTVHASGWNKILVPLVLLRQMLLELTRLGQEPLSALLQFGVTYLEDYSAEYIIQQGGWGTVFSLESEEEEYPGITAEDSNDIYILPSDNSGQVSPPESPTVTTSWQSESLPVSLSASQSWHTESLPVSLGPESWQQIAMDPEEVKSLDSNGAGEKSENNSSNSDIVHVEKEEVPEGMEEAAVASVVLPARELQEALPEAPAPLLPHITATSLLGTREPDTEVITVEKSSPATSLFVELDEEEVKAATTEPTEVEEVVPALEPTETLLSEKEINAREESLVEELSPASEKKPVPPSEGKSRLSPAGEMKPMPLSEGKSILLFGGAAAVAILAVAIGVALALRKK length: 386amino acids © Anne-Marie Ternes

PRIMARY STRUCTURE The numbers of amino acids vary (e.g. insulin 51, lysozyme 129, haemoglobin 574, gamma globulin 1250) The primary structure determines the folding of the polypeptide to give a functional protein Polar amino acids (acidic, basic and neutral) are hydrophilic and tend to be placed on the outside of the protein. Non-polar (hydrophobic) amino acids tend to be placed on the inside of the protein

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 = 10390 possible combinations Most are useless Natural selection picks out the best

SECONDARY STRUCTURE The folding of the N-C-C backbone of the polypeptide chain using weak hydrogen bonds © Science Student

SECONDARY STRUCTURE This produces the alpha helix and/or 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) © Dr Gary Kaiser

TERTIARY STRUCTURE The folding of the polypeptide into domains whose chemical properties are determined by the amino acids in the chain MIL1 protein © Anne-Marie Ternes

TERTIARY STRUCTURE 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) Hydrophobic amino acids tend to arrange themselves inside the molecule Hydrophilic amino acids arrange themselves on the outside

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

QUATERNARY STRUCTURE Some proteins are made of several polypeptide subunits (e.g. haemoglobin has four) Protein Kinase C © Max Planck Institute for Molecular Genetics

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 two, three or more levels

Result Protein structure depends upon the amino acid sequence This, in turn, depends upon the sequence of bases in the gene

PROTEIN FUNCTIONS Protein structure determines protein function Denaturation or inhibition which may change protein structure will change its function Coenzymes and cofactors in general may enhance the protein's structure

Fibrous proteins Involved in structure: tendons ligaments blood clots (e.g. collagen and keratin) Contractile proteins in movement: muscle, microtubules (cytoskelton, mitotic spindle, cilia, flagella)

Globular proteins Most proteins which aremoved around (e.g. albumen, casein in milk) Proteins with binding sites: enzymes, haemoglobin, immunoglobulins, membrane receptor sites

Proteins classified by function CATALYTIC: enzymes STORAGE: ovalbumen (in eggs), casein (in milk), zein (in maize) TRANSPORT: haemoglobin COMMUNICATION: hormones (eg insulin) and neurotransmitters CONTRACTILE: actin, myosin, dynein (in microtubules)

Proteins classified by function (contd) PROTECTIVE: Immunoglobulin, fibrinogen, blood clotting factors TOXINS: snake venom STRUCTURAL: cell membrane proteins, keratin (hair), collagen ENERGY

Polar and Non-Polar Amino Acids Amino acids can be polar or non-polar. Polar amino acids have R groups that do not ionize in solution but are quite soluble in water due to their polar character. They are also known as hydrophilic, or "water loving" amino acids. These include serine, threonine, asparagine, glutamine, tyrosine, and cysteine. The nonpolar amino acids include glycine, alanine, valine, leucine, isoleucine, methionine, proline, phenylalanine and tryptophan. Nonpolar amino acids are soluble in nonpolar environments such as cell membranes and are called hydrophobic molecules because of their "water fearing" properties.

Polar and Non-Polar Amino Acids The significance of.... Polar and Non-Polar Amino Acids Cell membrane proteins: Those sections of the molecule that contain polar amino acids are hydrophilic and can exist in contact with water. Polar amino acids allow the positioning of proteins on the external and internal surface of a cell membrane. Both cytoplasm and tissue fluid are water based regions. The non-polar amino acids allow the same protein to site within the phospholipid bilayer. The lining of the protein channel itself will be of polar amino acids to allow the diffusion of charged molecules and ions.  

Contd: The significance of.... Polar and Non-Polar Amino Acids Enzymes: Polar amino acids within the active site of an enzyme allow a chemical interaction between the substrate and the enzyme to form an activated complex. This transitional state allows the weakening of internal molecular structure and therefore the reduction of the activation energy.

Contd: The significance of.... Polar and Non-Polar Amino Acids