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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


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Volume 395, Issue 5

Issues

The structural biology of the amyloid precursor protein APP – a complex puzzle reveals its multi-domain architecture

Ina Coburger
  • Protein Crystallography Group, Leibniz Institute for Age Research-Fritz Lipmann Institute (FLI), Beutenbergstr. 11, D-07745 Jena, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Sandra Hoefgen
  • Protein Crystallography Group, Leibniz Institute for Age Research-Fritz Lipmann Institute (FLI), Beutenbergstr. 11, D-07745 Jena, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Manuel E. Than
  • Corresponding author
  • Protein Crystallography Group, Leibniz Institute for Age Research-Fritz Lipmann Institute (FLI), Beutenbergstr. 11, D-07745 Jena, Germany
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2014-02-07 | DOI: https://doi.org/10.1515/hsz-2013-0280

Abstract

The amyloid precursor protein (APP) and its processing are widely believed to be central for the etiology of Alzheimer’s disease (AD) and appear essential for neuronal development and cell homeostasis in mammals. Many studies show the proteolysis of APP by the proteases α-, β- and γ-secretase, functional aspects of the protein and the structure of individual domains. It is, however, largely unclear and currently also widely debated of how the structures of individual domains and their interactions determine the observed functionalities of APP and how they are arranged within the three-dimensional architecture of the entire protein. Further unanswered questions relate to the physiologic function of APP, the regulation of its proteolytic processing and the structural and functional effect of its cellular trafficking and processing. In this review, we summarize our current understanding of the structure-function-relationship of the multi-domain protein APP. This type-I transmembrane protein consists of the two folded E1 and E2 segments that are connected to one another and to the single transmembrane helix by flexible segments and likely fulfills several independent functions.

Keywords: 3D-Structure; Alzheimer’s disease; overall topology; structure-function-relationship

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About the article

Ina Coburger

Ina Coburger studied biochemistry at the Friedrich-Schiller-University in Jena, Germany and obtained her diploma in 2010. Since then she has worked on her PhD in the laboratory of Manuel E. Than at the Leibniz Institute for Age Research-Fritz Lipmann Institute (FLI). Her thesis is focused on structure-function relationships of APP.

Sandra Hoefgen

Sandra Hoefgen studied biology at the Friedrich-Schiller-University in Jena, Germany and obtained her diploma in 2009. Since then she has worked on her PhD in the laboratory of Manuel E. Than at the Leibniz Institute for Age Research-Fritz Lipmann Institute (FLI). Her thesis is focused on the dimerization behavior of APP.

Manuel E. Than

Manuel E. Than is currently independent junior group leader and head of the protein crystallography group at the Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI), Jena, Germany. He studied Chemistry and Biochemistry in Bayreuth, Germany and Delaware, USA. In 2000 he received his PhD from the TU Munich, Germany, for structural biology work in the department of Robert Huber at the Max-Planck-Institute of Biochemistry on transmembrane and soluble proteins of the energy metabolism. During his postdoctoral time with Wolfram Bode and his habilitation at the Gene Center of the Ludwig Maximilians University Munich he predominantly worked on the structural biology of proteases and methodological developments in protein crystallography. His group that he founded in 2006 focuses on X-ray crystallographic, biochemical and biophysical investigations of proteins involved in the development of Alzheimer’s disease and other aging-related processes.


Corresponding author: Manuel E. Than, Protein Crystallography Group, Leibniz Institute for Age Research-Fritz Lipmann Institute (FLI), Beutenbergstr. 11, D-07745 Jena, Germany, e-mail:


Received: 2013-11-15

Accepted: 2014-02-04

Published Online: 2014-02-07

Published in Print: 2014-05-01


Citation Information: Biological Chemistry, Volume 395, Issue 5, Pages 485–498, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2013-0280.

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Xi Peng, Francesco Emiliani, Philip M Smallwood, Amir Rattner, Hong Lei, Mark F Sabbagh, and Jeremy Nathans
eLife, 2018, Volume 7
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Lisa Dolfe, Simone Tambaro, Helene Tigro, Marta Del Campo, Jeroen J.M. Hoozemans, Birgitta Wiehager, Caroline Graff, Bengt Winblad, Maria Ankarcrona, Margit Kaldmäe, Charlotte E. Teunissen, Annica Rönnbäck, Jan Johansson, and Jenny Presto
Journal of Alzheimer's Disease Reports, 2018, Volume 2, Number 1, Page 27
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Lucas J. Sosa, Alfredo Cáceres, Sebastián Dupraz, Mariana Oksdath, Santiago Quiroga, and Alfredo Lorenzo
Journal of Neurochemistry, 2017
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Lukas P. Feilen, Kevin Haubrich, Paul Strecker, Sabine Probst, Simone Eggert, Gunter Stier, Irmgard Sinning, Uwe Konietzko, Stefan Kins, Bernd Simon, and Klemens Wild
Frontiers in Molecular Neuroscience, 2017, Volume 10
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Elena Montagna, Mario M. Dorostkar, and Jochen Herms
Frontiers in Molecular Neuroscience, 2017, Volume 10
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Klemens Wild, Alexander August, Claus U. Pietrzik, and Stefan Kins
Frontiers in Molecular Neuroscience, 2017, Volume 10
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Carole Deyts, Gopal Thinakaran, and Angèle T. Parent
Trends in Pharmacological Sciences, 2016, Volume 37, Number 5, Page 390
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Pedro Fernandez-Funez, Lorena de Mena, and Diego E. Rincon-Limas
Experimental Neurology, 2015, Volume 274, Page 58
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Christian Dienemann, Ina Coburger, Arnela Mehmedbasic, Olav M. Andersen, and Manuel E. Than
Biochemistry, 2015, Volume 54, Number 15, Page 2490
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Sven O. Dahms, Magnus C. Mayer, Dirk Roeser, Gerd Multhaup, and Manuel E. Than
Acta Crystallographica Section D Biological Crystallography, 2015, Volume 71, Number 3, Page 494
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Sandra Hoefgen, Sven O. Dahms, Kathrin Oertwig, and Manuel E. Than
Journal of Molecular Biology, 2015, Volume 427, Number 2, Page 433
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Edgar Dawkins, Robert Gasperini, Yanling Hu, Hao Cui, Adele J. Vincent, Marta Bolós, Kaylene M. Young, Lisa Foa, and David H. Small
Journal of Neuroscience Research, 2014, Volume 92, Number 11, Page 1478

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