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C483 Discussion Week of February 11 “Constitutive Activity of Glucagon Receptor Mutants” http://mend.endojournals.org/content/12/1/78.abstract Names: 1. _____________________________________ 2. ____________________________________ 3. _____________________________________ 4. ____________________________________ Questions: 1. (1pt) Glucagon is a polypeptide hormone with primary sequence HSQGTFTSDTSKYLDSRRAQDFVQWLMDT. What is its basic role in regulating blood sugar, and what hormone does it oppose? What is the net charge on glucagon at pH 7? 2. (1pt) (Refer to chapter 9.8B) What are the two major classes of integral membrane proteins? How are they structurally different? (1pt) Bacteriorhodopsin is in the same class of integral membrane proteins as glucoagon receptor, but they are in different families. List seven other proteins that are in the same family as glucagon receptor. What makes them all part of the same family? 3. (2pts) Use Figure 1 from the paper and chapter 9 from your text to draw a schematic of Glucagon Receptor embedded in a lipid bilayer. Use a ribbon structure for your protein, and head/tail cartoon for your lipid bilayer. Indicate the intracellular and extracellular domains. 4. (1pt) Consider the amino acids that are part of the secondary structures that are embedded in the cell membrane. What physical property do they generally share, and how is this important to the structure of the protein? What does 7TM stand for, and use the picture above to explain this term. 5. (1pt) Consider the structure/function relationship. The chemical function of the protein is to allow the cell to sense regulation hormones made in a different tissue, and then be able to change the internal chemistry of the cell. How does structure match function in this case? 6. (2pts) To quickly raise blood sugar, glucagon signals an enzyme that uses phosphate to clip one glucose residue off of the nonreducing side of glycogen, which is a polysaccharide of glucose residues linked (1 4). Draw this out structurally by filling in the boxes below. Glycogen is too long to draw the whole chain, but draw out 4 resides of glucose in a glycogen strand, with an end sugar that is on the non-reducing side. (See chapter 8 for help.) 7. (1pt) The author of this paper made seven mutants of glucagon receptor. One of them is H178R. What does that mean? What are the other mutants?