Structural biology

===Lecture Details===
Rob Pike; Week 2 MED1011; Biochemistry
===Lecture Content===
Red blood cells carry oxygen and carbon dioxide, primary function to transport gases. Sickle cells die faster and don't flow properly in circulation. 1:500 African Americans; 1:1000 Hispanic Americans, 1:12 African Americans carry the sickle cell trait (2 million Americans overall). Symptoms are anaemia (fatigue, pale skin, jaundice, SOB), pain from capillary blockage, various problems with specific organs due to capillary blockage. Treatment is with pain medication, hydroxyurea, prevention of infection, blood transfusions, bone marrow transplants.
Sickle cells have a greatly altered gas carrying capacity. The quartenary structure of haemoglobin is affected. Proteins in Hb have 4 levels of structure- primary structure of amino acid residues, secondary alpha helix structure, tertiary structure of a polypeptide chain, and quartenary structure of assembled subunits.
Amino acids contain amino group, carboxyl group, a central alpha carbon and a distinctive side chain or R group.
An alpha helix is formed when backbone atoms wind in a helical manner, H bonding is the most important stabilising feature. H from amino group in a peptide bond is H bonded to oxygen four residues away on carbonyl of another peptide bond.
Beta sheets are formed when backbone atoms are in a pleated conformation.
Tertiary structure of haemoglobin consists of 8 alpha-helices (70% of amino acids are in helices; assigned letters from A-H), has iron protoporhyrin (haem) group which binds oxygen, structure of protein is specifically adapted to provide a pocket for this group. Hydrophobic groups are hidden in the middle of a globular protein, In sickle cells, at position six in the amino acid sequence there is a point mutation from glutamate to valine on the A-helix. It changes the negatively charged, hydrophilic glutamate to the neutral, hydrophobic valine. Valine tends to clump together rather than interact with solvent inside cells. This produces a hydrophobic, sticky patch on the surface of the haemoglobin protein. It causes Hb S to form. The hydrophobic patches cause the proteins to associate with each other in the RBC, forming the fibres seen in the cells.
===Readings===
====Lehinger; 78-80, 88-89, 120-125, 132-135, 162-164, 172-174====