2LP1
The solution NMR structure of the transmembrane C-terminal domain of the amyloid precursor protein (C99)
Summary for 2LP1
| Entry DOI | 10.2210/pdb2lp1/pdb |
| NMR Information | BMRB: 15775 |
| Descriptor | C99 (1 entity in total) |
| Functional Keywords | amyloid precursor protein c-terminal fragment, alzheimer's disease, membrane protein, amyloid-beta precursor, transmembrane protein |
| Biological source | Homo sapiens (human) |
| Cellular location | Membrane; Single-pass type I membrane protein: P05067 |
| Total number of polymer chains | 1 |
| Total formula weight | 13801.77 |
| Authors | Barrett, P.J.,Song, Y.,Van Horn, W.D.,Hustedt, E.J.,Schafer, J.M.,Hadziselimovic, A.,Beel, A.J.,Sanders, C.R. (deposition date: 2012-01-30, release date: 2012-06-06, Last modification date: 2024-05-01) |
| Primary citation | Barrett, P.J.,Song, Y.,Van Horn, W.D.,Hustedt, E.J.,Schafer, J.M.,Hadziselimovic, A.,Beel, A.J.,Sanders, C.R. The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol. Science, 336:1168-1171, 2012 Cited by PubMed Abstract: C99 is the transmembrane carboxyl-terminal domain of the amyloid precursor protein that is cleaved by γ-secretase to release the amyloid-β polypeptides, which are associated with Alzheimer's disease. Nuclear magnetic resonance and electron paramagnetic resonance spectroscopy show that the extracellular amino terminus of C99 includes a surface-embedded "N-helix" followed by a short "N-loop" connecting to the transmembrane domain (TMD). The TMD is a flexibly curved α helix, making it well suited for processive cleavage by γ-secretase. Titration of C99 reveals a binding site for cholesterol, providing mechanistic insight into how cholesterol promotes amyloidogenesis. Membrane-buried GXXXG motifs (G, Gly; X, any amino acid), which have an established role in oligomerization, were also shown to play a key role in cholesterol binding. The structure and cholesterol binding properties of C99 may aid in the design of Alzheimer's therapeutics. PubMed: 22654059DOI: 10.1126/science.1219988 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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