by PhilipJ on 3 July 2006
Like Dr. Jekyll and Mr. Hyde, some seemingly innocent proteins have evil alter egos. The amyloid-beta precurson protein is an important example. It is a large membrane protein that normally plays an essential role in neural growth and repair. However, later in life, a corrupted form can destroy nerve cells, leading to the loss of thought and memory in Alzheimer’s disease.
Amyloid-beta precursor protein (APP) is a complicated protein with many functions. It is found on the surface of cells throughout the body. Like many membrane-tethered proteins, it is composed of several domains connected by flexible linkers, making it difficult to study as one intact piece. Looking to the PDB, we can find four pieces of APP, including three domains that extend on the outside of the cell (from top to bottom in blue, PDB entries 1mwp, 1owt, and 1rw6), and a special peptide that crosses the membrane (in green, from PDB entry 1iyt). There is also a small domain inside the cell, shown schematically here at the very bottom with a circle.
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