From: Protein Data Bank PDB ID: 1B0E Protein Structure Protein Structure From: Protein Data Bank PDB ID: 1B0E Kalus, W., Zweckstetter, M., Renner, C., Sanchez, Y., Georgescu, J., Grol, M., Demuth, D., Schumacher, R., Dony, C., Lang, K., Holak, T. A.: structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions. EMBO J 17 pp. 6558 (1998)

Functions Diverse functions related to structure Structural components of cells Motor proteins Enzymes Antibodies Hormones Hemoglobin/myoglobin Transport proteins in blood

Structure Amino acids Amino group (NH2) Carboxyl group (COOH) Proline has imino group rather than amino group

Amino acids 20 amino acids make up protein 8 essential amino acids (must be eaten in diet) 9 in infant (histidine) Zwitterion = double ion – when both NH3+ and COO- are ionised COO- can accept a proton, NH3+ can accept electron, so can act as acid and base (amphoteric)

Protein structure - bonding 5 bonds or forces determine structure Peptide bond Hydrogen bond Disulfide bond Ionic bond Hydrophobic force

Peptide bond Peptide bond joins amino acids Bond at both ends Increases range of possible proteins 1.0 x 1026 peptides can be formed from 20 amino acids Ability to form peptide bonds at both ends increases diversity of protein structure: 3 amino acids can make 6 possible peptides if only used once, but can make 27 if used more than once 20 different amino acids make up 1 x 1026 different arrangements if each used more than once Bonding in peptide chain blocks dissociable groups (NH2 and COOH). Ionized state of a protein therefore dependent on R groups.

condensation reaction

Primary protein structure Linear sequence of amino acids forms primary structure (long chain of amino acids) Sequence essential for proper physiological function

Sickle cell anemia Replacement of a single glutamine amino acid with valine in one chain of hemoglobin alters the structure and function of the protein Oxytocin and ADH only differ in primary structure by 2 amino acids, but Oxytocin induces contraction of uterus and milk ejection from mammary glands and ADH increases water reabsorption in the kidney and plays a role in the regulation of blood pressure.

Secondary protein structure Peptide chains fold into secondary structures to become more compact:  - helix  - pleated sheet

Alpha helix is a virtual solid cylinder Alpha helix is a virtual solid cylinder. There is almost no space along the axis, which makes it a very stable structure.

Alpha Helix

 - pleated sheet The term ‘ form’ came from the fact that it was first recognised in -keratin.

Beta Helix

Tertiary protein structure Secondary structures fold and pack together to form tertiary structure Usually globular shape Tertiary structure stabilized by bonds between R groups (i.e. sidechains) Bonds that stabilise tertiary structure are: hydrogen, disulfide, ionic and hydrophobic bonds Intracellular protein tertiary structures mostly held together by weak forces. Extracellular tertiary structures stabilised by disulfide (covalent) bonds.

Amino acid r-groups All amino acids contain a carboxyl group and an amino group. R-Groups distinguish between individual amino acids. R-Groups make them different from one another.

Tertiary structure - H bond Hydrogen bonds are weak electrical attractions between positively and negatively charged atoms of different molecules.

Tertiary structure - disulfide bond Covalent bond between sulfur atoms on two cysteine amino acids

Tertiary structure - ionic bond Ions on R groups form bridges through ionic bonds Ionic bonds form from the exchange of electrons between atoms Example: NaCl (table salt)

Tertiary structure - hydrophobic forces Close attraction of non-polar R groups in the chains Very weak but collective interactions over large areas help stabilize the protein structure

All bonds shown together

Quaternary protein structure The arrangement of many tertiary structures into one large protein molecule Not all proteins have or need a quaternary structure Allows for changes in structure/function in response to chemical stimuli