Crystal structure of the N-terminal, growth factor-like domain of Alzheimer amyloid precursor protein

  title={Crystal structure of the N-terminal, growth factor-like domain of Alzheimer amyloid precursor protein},
  author={Jamie Rossjohn and Roberto Cappai and Susanne C. Feil and Anna Henry and William J McKinstry and Denise Galatis and Lars Hesse and Gerd Multhaup and Konrad T. Beyreuther and Colin L. Masters and Michael W. Parker},
  journal={Nature Structural Biology},
Amyloid precursor protein (APP) plays a central role in Alzheimer disease. A proteolytic-breakdown product of APP, called β-amyloid, is a major component of the diffuse and fibrillar deposits found in Alzheimer diseased brains. The normal physiological role of APP remains largely unknown despite much work. A knowledge of its function will not only provide insights into the genesis of the disease but may also prove vital in the development of an effective therapy. Here we describe the 1.8… 
Three-dimensional structure of an independently folded extracellular domain of human amyloid-beta precursor protein.
An independently folded extracellular domain of human APP localized proximal to the Abeta sequence is identified, and the three-dimensional structure of this domain is determined by NMR spectroscopy.
Folding and Stability of the Extracellular Domain of the Human Amyloid Precursor Protein*
The relatively low stability of the native state of sAPPα suggests that conformational plasticity may play a role in allowing APP to interact with a number of distinct physiological ligands.
Structure and biochemical analysis of the heparin-induced E1 dimer of the amyloid precursor protein
The APP-based signal transduction, cell–cell- and/or cell–ECM interaction should depend on dimerization induced by heparin, as well as on pH, arguing that APP could fulfill different functions depending on its (sub)cellular localization.
The structural biology of the amyloid precursor protein APP – a complex puzzle reveals its multi-domain architecture
Current understanding of the structure-function-relationship of the multi-domain protein APP, which consists of the two folded E1 and E2 segments that are connected to one another and to the single transmembrane helix by flexible segments, is summarized.
The amyloid precursor protein shows a pH-dependent conformational switch in its E1 domain.


A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth
  • D. Small, V. Nurcombe, C. Masters
  • Biology, Chemistry
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1994
Results indicate that the binding of APP to HSPG in the ECM may stimulate the effects of APP on neurite outgrowth.
The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
An apparently full-length complementary DNA clone coding for the A4 polypeptide is isolated and sequenced and suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor.
Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives.
Alternative enzymatic processing of beta-APP liberates A beta, which has a propensity to form amyloid fibrils; A beta can damage and kill neurons and increase their vulnerability to excitotoxicity.
Ligand-dependent G Protein Coupling Function of Amyloid Transmembrane Precursor (*)
In phospholipid vesicles consisting of baculovirally made APP695 and brain trimeric Go, 22C11, a monoclonal antibody against the extracellular domain of APP, increased GTPγS binding and the turnover number of GTPase of Go without affecting its intrinsic GTP enzyme activity.
Interaction of the Phosphotyrosine Interaction/Phosphotyrosine Binding-related Domains of Fe65 with Wild-type and Mutant Alzheimer's β-Amyloid Precursor Proteins*
A role for Fe65 in the pathogenesis of familial Alzheimer's disease is suggested by the finding that mutant APP shows an altered in vivo interaction with Fe65, as demonstrated by anti-Fe65 co-immunoprecipitation experiments.
Intrinsic signaling function of APP as a novel target of three V642 mutations linked to familial Alzheimer's disease.
The intrinsic signaling function of APP is identified to be a novel target of hereditary Alzheimer's disease mutations, providing an in vitro system for the screening of potential FAD inhibitors.