Download Beta-amyloid precursor protein

Beta-amyloid
precursor protein
Hydropathy plot
Membrane Bound
Sequence Alignment
Sequence Alignment
Beta-secretase cut site
19F and 20F
AA 41 and 42
Extracellular Domain
(1mwp)
(1owt)
Beta Sheets = green
Alpha Helices = purple
Links between regions color coded
(1rw6)
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
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
Membrane (Tertiary structure)
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.
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
Alzheimer’s disease(2beg)
• Linked to buildup of
amyloid-beta
plaques
• Form complex betasheet fibrils
Alzheimer’s disease
• Tertiary structure of the
Amyloid beta plaque
– All Beta Sheets and
linkers
– Insoluble in cytosol and
polar solvents.
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, 323-349.
• 2.) Berhanu, W. M., and Hansmann, U. H. E. (2012) Side-chain
hydrophobicity and the stability of Aβ16–22 aggregates. Protein Sci.
v21(12), 1837-1848.
• 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: 10.1046/j.14321033.2002.03271.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), 498-512.