4dbb

The PTB domain of Mint1 is autoinhibited by a helix in the C-terminal linker regionThe PTB domain of Mint1 is autoinhibited by a helix in the C-terminal linker region

Structural highlights 4dbb is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , Gene: APBA1, Mint1, X11 (Rattus norvegicus) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Mint adaptor proteins bind to the amyloid precursor protein (APP) and regulate APP processing associated with Alzheimer's disease; however, the molecular mechanisms underlying Mint regulation in APP binding and processing remain unclear. Biochemical, biophysical, and cellular experiments now show that the Mint1 phosphotyrosine binding (PTB) domain that binds to APP is intramolecularly inhibited by the adjacent C-terminal linker region. The crystal structure of a C-terminally extended Mint1 PTB fragment reveals that the linker region forms a short alpha-helix that folds back onto the PTB domain and sterically hinders APP binding. This intramolecular interaction is disrupted by mutation of Tyr633 within the Mint1 autoinhibitory helix leading to enhanced APP binding and beta-amyloid production. Our findings suggest that an autoinhibitory mechanism in Mint1 is important for regulating APP processing and may provide novel therapies for Alzheimer's disease. Autoinhibition of Mint1 adaptor protein regulates amyloid precursor protein binding and processing.,Matos MF, Xu Y, Dulubova I, Otwinowski Z, Richardson JM, Tomchick DR, Rizo J, Ho A Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3802-7. Epub 2012 Feb 21. PMID:22355143 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4dbb, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image