1. Beta-amyloid precursor protein

2. Hydropathy plot
Membrane Bound

3. Sequence Alignment

4. Sequence Alignment
Beta-secretase cut site
19F and 20F
AA 41 and 42

5. Extracellular Domain (1mwp) (1owt) Beta Sheets = green
Alpha Helices = purple
Links between regions color coded
(1rw6)

6. Extracellular Domain
Not much is known about the extracellular domain function.
Somewhat involved with neural growth and plasticity.
Found in many different cells throughout the body

7. Membrane Domain (1iyt)
Membrane Domain is composed of two helices and turn in between
Quaternary structure has overlapping alpha helices
Green = amino acids 41 and 42

8. Membrane (Tertiary structure)

9. Beta-secretase (2fkn)
Aspartyl protease that clips APP at the start of the membrane domain
Yellow = beta sheets
Pink = alpha helices
Asp 32 and 215 are the active site proteases.

10. Side-chain interaction of Amyloid-Beta domain (1iyt)
Adjacent phenylalanine residues provide hydrophobic π-stacking interactions
There is also a salt bridge formed by K16 and D22
Phe 20
Phe 19

11. Alzheimer’s disease(2beg)
Linked to buildup of amyloid-beta plaques
Form complex beta-sheet fibrils

12. Alzheimer’s disease Tertiary structure of the Amyloid beta plaque
All Beta Sheets and linkers
Insoluble in cytosol and polar solvents.

13. References
1.) C. Morgan, M. Colombres, M. T. Nunez & N. C. Inestrosa (2004) Structure and function of amyloid in Alzheimer's disease. Progress in Neurobiology 74,
2.) Berhanu, W. M., and Hansmann, U. H. E. (2012) Side-chain hydrophobicity and the stability of Aβ16–22 aggregates. Protein Sci. v21(12),
3.) Crescenzi, O., Tomaselli, S., Guerrini, R., Salvadori, S., D'Ursi, A. M., Temussi, P. A. and Picone, D. (2002), Solution structure of the Alzheimer amyloid β-peptide (1–42) in an apolar microenvironment. European Journal of Biochemistry, 269: 5642–5648. doi:  /j x
4.) Petkova, A. T., Yau, W., and Tycko, R., (2006) Experimental constraints on quaternary structure in Alzheimer's β-amyloid fibrils. NIHPA Biochemistry. 45(2),