Sandbox Reserved 591: Difference between revisions

The extracellular region is separated into the E1 and E2 domains which are linked by an acidic domain. Over 70 percent of the amino acid residues of this region are involved with standard secondary structure elements. As shown in Figure 1, the amyloid beta peptide can be shown in two guises where the structure on the left shows how the peptide might look when it interacts with the membrane. A majority of it is folded into an alpha helix. The structure on the right displays the form in the amyloid fibril where thousands of peptides stack on top of each other to make an extensive beta sheet. APP is a type I transmembrane that separates the large N-terminal extracellular domain from the short C-terminal cytoplasmic tail domain. The N-terminal, crystalized in 1999, contains nine beta-strands and only one alpha-helix. The domain has a surplus of cysteine and has three disulfide bridges and a hydrophobic core which together are well conserved throughout the APP family. The disulfide bridge between Cys98 and Cys105 stabilizes a β-hairpin loop which appears to be essential for neurite development and MAP kinase activation. This surface possibly represents one of the APP heparin-binding sites. Although, the β-hairpin loop is the most mobile area in this structure. <ref>Reinhard,Constanze. 2005. The amyloid-bold beta precursor protein: integrating structure with biological function. EMBO 24: 3996 - 4006.</ref>. Adjacent to this heparin structure is a hydrophobic surface patch which is critical in protein-protein interactions. The N-terminal head domain of APP has nothing in common with any other known protein. Since this structure can initiate neurite growth, some scientists think the N-terminal head domain alone is responsible for growth-factor like characteristics of APP. However, further exploration is needed to confirm this hypothesis. <ref>PMID:1356301</ref>.