TY - CONF A1 - Bierkandt, Frank A1 - Reichardt, Ph. A1 - Haase, A. A1 - Jungnickel, H. A1 - Tentschert, J. A1 - Pfaff, K. A1 - Luch, A. A1 - Jakubowski, Norbert T1 - Laserablation-ICP-MS analysis of cell lysates after silver nanoparticle treatment: Is quantification possible? T2 - European Winter Conference on Plasma Spectrochemistry CY - Kraków, Poland DA - 2013-02-10 PY - 2013 AN - OPUS4-28036 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Bierkandt, Frank A1 - Müller, Larissa A1 - Techritz, Sandra A1 - Jakubowski, Norbert A1 - Roos, Peter H. A1 - Linscheid, M. T1 - Quantitative Analyse phosphorylierter Proteine mittels LA-ICP-MS T2 - 46. Jahrestagung der Deutschen Gesellschaft für Massenspektrometrie CY - Berlin, Germany DA - 2013-03-10 PY - 2013 N1 - Geburtsname von Müller, Larissa: Wäntig, L. - Birth name of Müller, Larissa: Wäntig, L. AN - OPUS4-28038 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Bierkandt, Frank A1 - Jakubowski, Norbert A1 - Linscheid, M. T1 - Quantitative Analysis of Phosphorylated Proteins with LA-ICP-MS T2 - European Winter Conference on Plasma Spectrochemistry 2013 CY - Kraków, Poland DA - 2013-02-10 PY - 2013 AN - OPUS4-27898 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Bierkandt, Frank A1 - Reichardt, Ph. A1 - Haase, A. A1 - Jungnickel, H. A1 - Tentschert, J. A1 - Luch, A. A1 - Jakubowski, Norbert T1 - Quantitative Analyse der Silbernanopartikelaufnahme durch Zellen mittels LA-ICP-MS T2 - Adlershofer Forschungsforum CY - Berlin, Germany DA - 2013-11-12 PY - 2013 AN - OPUS4-29551 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Munter, L.M. A1 - Sieg, H. A1 - Bethge, T. A1 - Liebsch, F. A1 - Bierkandt, Frank A1 - Schleeger, M. A1 - Bittner, H.J. A1 - Heberle, J. A1 - Jakubowski, Norbert A1 - Hildebrand, P.W. A1 - Multhaup, G. T1 - Model peptides uncover the role of the beta-secretase transmembrane sequence in metal ion mediated oligomerization N2 - The β-secretase or β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the enzyme responsible for the formation of amyloid-β peptides, which have a major role in Alzheimer pathogenesis. BACE1 has a transmembrane sequence (TMS), which makes it unique among related proteases. We noticed that the BACE1 TMS contains an uncommon sulfur-rich motif. The sequence MxxxCxxxMxxxCxMxC spans the entire TMS, resembles metal ion binding motifs, and is highly conserved among homologues. We used a synthetic 31-mer model peptide comprising the TMS to study metal ion binding and oligomerization. Applying diverse biochemical and biophysical techniques, we detected dimer and trimer formation of the TMS peptide with copper ions. Replacement of the central Cys466 by Ala essentially abolished these effects. We show that the peptide undergoes a redox reaction with copper ions resulting in a disulfide bridge involving Cys466. Further, we find peptide trimerization that depends on the presence of monovalent copper ions and the sulfhydryl group of Cys466. We identified Cys466 as a key residue for metal ion chelation and to be the core of an oligomerization motif of the BACE1-TMS peptide. Our results demonstrate a novel metal ion controlled oligomerization of the BACE1 TMS, which could have an enormous therapeutic importance against Alzheimer disease. KW - Enzymes KW - Amyloid formation KW - Alzheimer disease KW - Copper PY - 2013 U6 - https://doi.org/10.1021/ja410812r SN - 0002-7863 SN - 1520-5126 VL - 135 IS - 51 SP - 19354 EP - 19361 PB - American Chemical Society CY - Washington, DC AN - OPUS4-30543 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -