Please help with this bio chem, and add explanations please! 2. Amyloid aggregat
ID: 190723 • Letter: P
Question
Please help with this bio chem, and add explanations please!
2. Amyloid aggregation (34 points). Amyloid is a protein associated with Alzheimer's disease that aggregates into repeating sandwich structures. One type of amyloid aggregate involving amino acids 17-41 is shown below in both ribbon and space filling depictions (Luhrs et al. PNAS, 2005): 2 S26 "odd" end V24 E2 F20 N27 25 V18 G29 "K28' D23 ' A30 L34 A21 V36 F19 131 17 G38 V40 M35 G37 Fibril Axis V39 D23 B1 "odd" end 141 a) Amino acids 26-30 form a loop that connects the two strands. Compare the chemical properties of these sidechains to those of the amino acids 31-41 referencing specific functional groups in your comparison. Is this difference between these two regions expected? Why or why not? (2-3 sentences) b) The K28 sidechain faces into the interior of the sandwich rather than toward the protein exterior. Why would we generally not expect to see a lysine sidechain on the interior of a sandwich? (1 sentence) c) Propose a mutation to amino acid 19 designed to disrupt aggregation of this protein. Justify your choice (1-3 sentences) d) Why is the orientation observed for this lysine sidechain favorable in this particular sheet? (1-3 sentences)Explanation / Answer
a) Glycine and Proline are observed in Beta turns, the former one is present because it is small and flexible and the latter because peptide bonds involving the nitrogen (imino) of proline readily assume the cis confirmation (which is formed because of the connecting loop). But mostly inside the beta sheets the glycine or alanine are found because of the presence of no functional group or smallest functional groups with no bulky group. They take part in many confirmation that are sterically hindered because of other amino acids.
b) Lysine has got a long chain functional group and an amino group at its end. So if the orientation is towards the interior, then that would definitely disrupt the structure of the protein. The open amino end is likely to react with the interior structure.
c) In F19, an aromatic amino acid is present. So, to disrupt the confirmation, any type of bulky amino acid, with huge functional group would help.
d) I couldn't understand this question.