APP to scale. (a,b) APP is an integral membrane-bound protein, comprising a large extracellular region, a single transmembrane helix and a short cytoplasmic tail referred to as the AICD, that contains a highly conserved NPxY motif. The largest isoform, APP770 is shown. (a) The unfurled AlphaFold structural model shows the structured domains in the context of the entire molecule. (b) Cartoon representation of (a), the colour coding for the domains is used in all the schematics. The scale bars show the lengths of the linker regions. (c) The structural model of APP as downloaded from AlphaFold (UniProt ID: P05067). (d,e) APP in the context of the membrane. (d) The unfurled AlphaFold model from (c) shown embedded in the plasma membrane, showing the dimensions of the protein and arrangement of the domains relative to each other and the membrane. (e) Cartoon representation of (d). (f) Sequence alignment of the human cytoplasmic tails of APP and integrins β1A, β1D and β3. A blue line shows the NPxY-containing YENPTY motif.