NAME: ID # BME50A – EXAM 1 – January 21, 2015 – 40 minutes (While I don’t expect a major time crunch, you should still think intensely and work briskly. Please use a pen. Use your scratch paper to work out your answer before writing it on the test. If you must cross out an answer on the test, you can write the answer on the back of that page, provided you note it clearly.) Question 1 (20 points): For the following statements, circle TRUE or FALSE or LEAVE IT BLANK. (For each correct choice, you will receive 2 points. For each incorrect choice, you will lose 2 points. For each choice left blank, you will neither receive or lose points.) a) By reading the hydrogen bonding patterns in the minor groove of duplex DNA, it is possible to distinguish all four possible base pairs (AT, TA, CG, GC) from each other. TRUE FALSE b) Rotation around a carbon-carbon double bond takes much more energy than rotation around a carbon-carbon single bond. TRUE FALSE c) Ionic bonds between two ions are much stronger in water than in air. TRUE FALSE d) A nucleosome contains a stretch of double-stranded DNA wrapped around a single histone protein. TRUE FALSE e) The four peptide chains of an antibody are held together by disulfide bonds. TRUE FALSE f) Telomeres contain repeated nucleotide sequences. TRUE FALSE g) Protein phosphatases are enzymes that add a phosphate group to a cognate protein. TRUE FALSE h) The phospholipids in the plasma membrane are amphipathic. TRUE FALSE i) The addition of cholesterol into a human cell’s plasma membrane increases the fluidity of the membrane. TRUE FALSE j) When a molecule of glucose and a molecule of fructose join to form the disaccharide sucrose, two molecules of water are lost. TRUE FALSEQuestion 2 (20 points): At high enough temperatures, duplex DNA melts, meaning that the Watson-Crick base pairs break apart. This is called the melting temperature of DNA. For example, if I boil a duplex DNA sequence such as ATCCATTAG, I will get two single strands of DNA: ATCCATTAG and CTAATGGAT. a) Consider the following sequences of duplex DNA. Which has the higher melting temperature? Why? Circle the one with the higher melting temperature and explain your choice. (4 points) ATAATTT OR CAGTAAC Explanation (One sentence max. We will only grade your first sentence.): The second sequence has more hydrogen bonds due to more C-G pairs. b) Consider the following sequences of duplex DNA. Which has the higher melting temperature? Why? Circle the one with the higher melting temperature and explain your choice. (4 points) ATAATTA OR ATAATTAAA Explanation (One sentence max. We will only grade your first sentence.): The second sequence has more hydrogen bonds due to more base pairs. c) Now consider the following system where all A’s are replaced with a nucleotide called X. X is like A but has an extra ring in the middle. Just like A, X hydrogen bonds to T, as shown. Consider the following sequences of duplex DNA. Which has the higher melting temperature? Why? Circle the one with the higher melting temperature and explain your choice. (12 points) XTXTTXX OR XTXCGXX Explanation (Two sentences max. We will only grade your first two sentences.): X-T pairs increase the overall diameter of the duplex DNA such that the distance between Cs and Gs is too far for hydrogen bonds to form in the second sequence. Since all Xs and Ts in the first sequence form hydrogen bonds with each other, the first sequence has a higher melting temperature.Question 3 (30 points): To refresh your memory, below is the structure of an alpha-helix (R denotes amino acid sidechains). a) As drawn, what direction is N to C? Top to bottom or bottom to top? (5 points) Top to bottom. b) Alpha helices with fewer than five amino acids aren’t stable. Why? (Two sentences max. We will only grade your first two sentences.) (10 points) Alpha helices are stabilized by the i+4 hydrogen bonding. A peptide with 4 or less amino acids cannot hydrogen bond to form a stable alpha helix. c) Molecule X, when linked to the N-terminus of an alpha helix peptide in the manner shown, significantly promotes the rate of helix formation. Why? (Feel free to annotate the molecule and refer to your annotations in your answer. Three sentences max. We will only grade your first three sentences.) (Hint: answer part (b) first.) (15 points) Molecule X provides additional carbonyl groups to initiate alpha helix formation by forming hydrogen bonds with the amine hydrogens of the first and second amino acids. The hydrogen bonds are shown as dashed red lines in the diagram.Question 4 (30 points): a) Proteins that span the lipid bilayer must expose predominantly nonpolar sidechains to the membrane. However, the peptide backbone itself has polar groups in it! Clearly, these need to get at least partially masked to avoid the potentially disfavorable interaction with lipids. With this in mind, please explain why alpha-helices are much more commonly found crossing the membrane than beta-sheets. (There is an image of an alpha helix in question 3. Three sentences max. We will only grade your first two sentences.) (12 points) The polar groups (amines and carbonyls) in a peptide backbone is masked in an alpha helix through the i+4 hydrogen bonding. However, it is difficult to mask those polar groups in beta-sheets. While the internal beta-sheets form hydrogen bonds on both sides, the external beta sheets only form hydrogen bonds on one side, exposing polar groups on the other side. b) There is one exceptional class of beta-sheet proteins that do in fact span the lipid bilayer. These are the beta-barrel proteins, which are some of the most beautiful transmembrane proteins around. (See example on the left.) Of the following sequences, which is most likely to correspond to the partial sequence of one of the beta-sheet segments spanning the membrane? Circle the most likely sequence and explain your choice. (12 points) Seq 1: …Tyr Val Trp Met Leu Asp Lys Asn Asp Arg… Seq 2: …Tyr Asp Val Lys Trp Asn Met Asp Leu Arg… Seq 3: …Tyr Val Asp Lys Trp Met Asn Asp Leu Arg… Seq 4: …Tyr Val Trp Asp Lys Asn Met Leu Arg Asp... Explanation (Two sentences max. We will only grade your first two sentences): Beta sheets have alternating side chains that point towards opposite sides. Beta sheets with alternating hydrophobic and hydrophilic residues