Download Amyloid precursor

When Good Proteins Go Bad…
The Amyloid Precursor Protein, its Functions and Dysfunctions
Caitlin “Bio Queen” Mecum
Rachael “Handmaiden” Sondeno
John “Wiegeabo” Victor
Kirk “Keyboard Jockey” Van Gorkom
CSUS Bioinformatics Winter 2002
Protein Stats
Name: Amyloid Precursor Protein
AKA: APP
Last known location: In your brain
DNA location: Chromosome 21, 11, & 19
Common Disguises (isoforms): 695, 751, 770 AA, based on alternative splicing
Known Hangouts: neuronal tissue (695), other disguises are found throughout the body
Convictions and Acquittals (Exons & Introns): 16 & 15, respectively
May be considered armed and dangerous if you cut him wrong.
TMAP Findings:
Predicts transmembrane segments.
APP only spans the cell membrane once.
Amino acid segments 624-652 are predicted to cross the membrane threshold.
GREASE Findings:
Troubled Childhood (evolution)
Legal Activities
When on the job, APP acts as a functional neuronal receptor and communications
engineer. APP plays a role in intracellular signaling by regulating cell-cell or cellsubstrate interactions.
As a receptor it binds to metals (Zn, Fe, Cu), clathrin, and heparin.
Involved with synaptogenesis (formation and growing of new neural pathways).
Past Employment (Normal Functions)
Normally, APP clips itself using two different pathways, -secretase and  - secretase.
Following the -secretase pathway, APP is clipped between amino acids 612 and 613,
or between the 16th and 17th amino acids with regards to the A protein. A full-length
version of A is not formed.
The -secretase pathway clips APP between amino acids 596 and 597 and is followed
by a presenilin-1 regulated -secretase pathway that clips the A protein at amino
acid 40. This forms a full-length A protein (A 1-40).
Both - and - pathways normally do not engage in criminal activity.
Most Recent Good Mugshot
Most Recent Good Mugshot
Criminal Activities
Deviant behavior can lead to major system malfunctions.
Definition: missense – a change in a codon that results in a
acid
different amino
A mutation in the presenilin-1 gene found in FAD can lead to 42 clipping, or an
A1-42 protein.
Known as Swedish FAD missense, a mutation 2 amino acids before the normal A140 region can increase the likelihood of plaque formation.
A Flemish-Dutch FAD missense alters the -secretase cleavage pathway which can
lead to a protein more likely to aggregate.
The British FAD missense involves a mutation after the normal A1-40 region which
results in an abnormal A1-44.
Consequences of Deviant Behavior
Normal A1-40 protein formation will result in an -helical structure. However,
mutated versions, especially A1-42, tend to form -sheets. These -sheets like to
clump together and precipitate which can lead to the formation of plaques.
Formation of plaques can also be influenced by interaction with A by metals such as
aluminum, zinc, copper, and iron.
References
Clippingdale AB, Wade JD, Barrow CJ. Amyloid-β peptide and its role in
Alzheimer’s disease. Journal of Peptide Science 2001; 7: 227-249
Coulson EJ, Paliga K, Beyreuther K, Masters, CL. What the evolution of the
amyloid protein precursor supergene family tells us about its function.
Neurochemistry International 2000; 36(3): 175-184.
Diehlmann A., Ida N., Weggen S., Grunberg J., Haass C., Masters CL, Bayer
TA, Beyreuther K. Analysis of presenilin 1 and presenilin 2 expression and
processing by newly developed monoclonal antibodies. Journal of Neuroscience
Research 1999; 56: 405-419.
Kienlen-Campard P., Tasiaux B., Octave JN. The processing and biological
function of the human amyloid precursor protein in functional synapse formation
in cultured hippocampal neurons. Experimental Gerontology 2000; 35(6-7): 843850.
Morimoto T, Ohsawa I, Takamura C, Ishiguro M, Kohsaka S. Involvement of
amyloid precursor protein (APP): lessons from different cellular models. Journal
of Neuroscience Research 1998; 51: 185-195.
Biology Workbench at SDSC http://workbench.sdsc.edu
NCBI Entrez at http://www.ncbi.nlm.nih.gov
Tools used in the Workbench: Ndjinn, TMAP, GREASE, CLUSTALW, BLASTP,
SWISSPROT
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