University of Groningen
Structural and biochemical characterization of Roco proteins Terheyden, Susanne
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Publication date: 2018
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Terheyden, S. (2018). Structural and biochemical characterization of Roco proteins. University of Groningen.
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Structural and Biochemical Characterization of
Roco Proteins
PhD Thesis
Susanne Terheyden
The research described in this thesis was carried out at the Department of Cell Biochemistry of the Graduate School of Science and Engineering (GSSE) of the University of Groningen and at the Max Planck Institute of Molecular Physiology in Dortmund. This research was funded by the Michael J. Fox Foundation for Parkinson research (MJFF) and the GSSE.
ISBN: 978-94-034-0475-2
© Copyright 2018 Susanne Terheyden
All rights reserved. No part of this thesis can be reproduced, stored in a retrieval system or transmitted in any form of means, without prior written permission of the author and the publisher holding the copyright of the articles.
Cover design: Susanne Terheyden
Structural and Biochemical
Characterization of Roco
Proteins
PhD thesis
to obtain the degree of PhD at the University Groningen 0n the authority of the Rector Magnificus Prof. E. Sterken
and in accordance with
the decisions by the College of Deans. This thesis will be defended in public on
Friday, 25th of May 2018 at 16:15 hours
by
Susanne Terheyden
born on the 11th of April 1988
Supervisor
Prof. dr. P.J.M. van Haastert
Co-supervisor
Dr. A. Kortholt
Em. prof. dr. A. Wittinghofer
Assessment Committee
Prof. dr. F.W. Herberg Prof. dr. B. Poolman Prof. dr. D.B. Janssen
Contents
Chapter 1
Introduction: The unconventional G-protein cycle of LRRK2 and Roco proteins Aims of the Thesis
7 15
Chapter 2
Revisiting the Roco G-protein cycle 17
Chapter 3
A homologue of the Parkinson’s disease-associated protein LRRK2 undergoes a
monomer-dimer transition during GTP turnover 29
Chapter 4
Biochemical and kinetic properties of the complex Roco G-protein cycle 61
Chapter 5
Structural insights into the Roco G-protein cycle 89
Chapter 6
Regulation of LRRK2 activation, localization and dimerization 119
Chapter 7
Summary and Discussion 149
Nederlandse Samenvatting 158
