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Nouveaux développements en biologie structurale basés sur des complexes de lanthanide

Abstract : Since the first protein structure determined in the 1950s, X-ray crystallography emerged as a method of choice to obtain structural data at atomic resolution. Despite technological advances such as new synchrotron sources, hybrid pixel detectors, and high-performance softwares, obtaining an electron density map of a biological macromolecule is always limited by two major bottlenecks namely, producing high quality single crystals and solving the phase problem.This thesis presents a new lanthanide complex called “Crystallophore” (Tb-Xo4). This compound has been developed in collaboration with Olivier Maury and François Riobé of the Laboratoire de chimie Matériaux Fonctionnels et Photonique (ENS –Lyon). The design of this new complex is based on fifteen years of development in the field of structural biology. This thesis highlights the effects of Tb-Xo4 on the crystallisation and the structure determination of biological macromolecules. Indeed, the addition of Tb-Xo4 to a protein solution induces a large number of new and unique crystallization conditions. The analysis of the structures of several proteins co-crystallized with Tb-Xo4 allowed both, to highlight the high phasing power of Tb-Xo4 but also to describe finely the supramolecular interaction of the complex with the macromolecules. This work led to protocols dedicated to crystallization and phasing assisted with Tb-Xo4. Finally, this thesis leads to a model explaining the unique properties of this new lanthanide complex.
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Submitted on : Friday, June 22, 2018 - 12:15:15 PM
Last modification on : Tuesday, October 6, 2020 - 4:12:09 PM
Long-term archiving on: : Monday, September 24, 2018 - 5:59:51 PM


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  • HAL Id : tel-01821177, version 1



Sylvain Engilberge. Nouveaux développements en biologie structurale basés sur des complexes de lanthanide. Biochimie, Biologie Moléculaire. Université Grenoble Alpes, 2017. Français. ⟨NNT : 2017GREAY094⟩. ⟨tel-01821177⟩