Metal Binding Dictates Conformation and Function of the Amyloid Precursor Protein APP E2 Domain

AbstractThe amyloid precursor protein (APP) and its neurotoxic cleavage product Aβ are key players in the development of Alzheimer's disease and appear essential for neuronal development and cell homeostasis in mammals. Proteolytic processing of APP is influenced by metal ions, protein ligands and its oligomerization state. However, the structural basis and functional mechanism of APP regulation are hitherto largely unknown. Here we identified a metal-dependent molecular switch located within the E2 domain of APP containing four evolutionary highly conserved histidine residues. Three X-ray structures of the metal-bound molecule were solved at 2.6–2.0 Å resolution. Using protein crystallographic and biochemical methods, we characterized this novel high-affinity binding site within the E2 domain that binds competitively to copper and zinc at physiological concentrations. Metal-specific coordination spheres induce large conformational changes and enforce distinct structural states, most likely regulating the physiological function of APP and its processing in Alzheimer's disease

Ultrafast Optical Demagnetization manipulates Nanoscale Spin Structure in Domain Walls

During ultrafast demagnetization of a magnetically ordered solid, angular momentum has to be transferred between the spins, electrons, and phonons in the system on femto and picosecond timescales. Although the intrinsic spin transfer mechanisms are intensely debated, additional extrinsic mechanisms arising due to nanoscale heterogeneity have only recently entered the discussion. Here we use femtosecond X ray pulses from a free electron laser to study thin film samples with magnetic domain patterns. We observe an infrared pump induced change of the spin structure within the domain walls on the sub picosecond timescale. This domain topography dependent contribution connects the intrinsic demagnetization process in each domain with spin transport processes across the domain walls, demonstrating the importance of spin dependent electron transport between differently magnetized regions as an ultrafast demagnetization channel. This pathway exists independent from structural inhomogeneities such as chemical interfaces, and gives rise to an ultrafast spatially varying response to optical pump pulse

X-ray holography

With the dramatic increase in x-ray source brilliance and associated coherent photon flux, holography with x-rays has become feasible and is increasingly used for real-space investigations of static and dynamic properties of nanoscale systems. We describe the basic principles and capabilities of the method and present the current state of the art. A particular emphasis is put on the investigation of magnetic nanostructures, where x-ray holography has been applied at synchrotron radiation sources and free-electron x-ray lasers to investigate dynamic effects on time scales down to the femtosecond regime

X-ray holography

With the dramatic increase in x-ray source brilliance and associated coherent photon flux, holography with x-rays has become feasible and is increasingly used for real-space investigations of static and dynamic properties of nanoscale systems. We describe the basic principles and capabilities of the method and present the current state of the art. A particular emphasis is put on the investigation of magnetic nanostructures, where x-ray holography has been applied at synchrotron radiation sources and free-electron x-ray lasers to investigate dynamic effects on time scales down to the femtosecond regime