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NMR Spectroscopy of very large complexes: the atomic details of the mRNA degradation machinery

Objective

The cellular environment is extremely complex and contains thousands of different bio-molecules. To determine how these bio-molecules assemble into a highly organized molecular system has remained a major challenge. Here, we aim to unravel how dozens of proteins assemble into a large molecular machinery that degrades mRNA in an efficient and regulated manner.

On an atomic level, we will determine the static structures of the enzymes involved in the mRNA degradation pathways. In parallel, we will develop and exploit novel methods in NMR spectroscopy to correlate molecular motions with catalytic activity. Especially for the 450 kDa eukaryotic exosome complex, these studies will significantly push the limits of what is currently achievable. On a molecular level, we will reconstitute the mRNA degradation machinery from purified components in a stepwise manner. In this challenging approach, we will use NMR spectroscopy to follow how the enzymes engage in a network of interactions that regulate the mRNA degradation process. These studies will also provide us with the unique possibility to reproduce complex cellular behavior in a well defined and easy to manipulate in vitro system. On a microscopic level the mRNA degradation machinery assembles into cytoplasmic processing bodies. The role of these conserved cellular foci is a matter of debate and we aim to determine both the atomic details that result in this self-organization as well as the catalytic advantages that result from this clustering.

Our study will provide a very detailed and accurate description of how essential and central molecular processes in mRNA degradation are regulated and modulated. The level of detail that we aim to achieve is currently not available for any cellular pathway of such complexity. In that regard, our projects also provide knowledge and methodology required to study additional and complex cellular functions.

Field of science

  • /natural sciences/chemical sciences/analytical chemistry/spectroscopy
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/biological sciences/biochemistry/biomolecules
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes

Call for proposal

ERC-2013-CoG
See other projects for this call

Funding Scheme

ERC-CG - ERC Consolidator Grants

Host institution

UNIVERSITAET REGENSBURG
Address
Universitatsstrasse 31
93053 Regensburg
Germany
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 089 318,89
Principal investigator
Remco Sprangers (Dr.)
Administrative Contact
Matthias Köhler (Dr.)

Beneficiaries (2)

UNIVERSITAET REGENSBURG
Germany
EU contribution
€ 1 089 318,89
Address
Universitatsstrasse 31
93053 Regensburg
Activity type
Higher or Secondary Education Establishments
Principal investigator
Remco Sprangers (Dr.)
Administrative Contact
Matthias Köhler (Dr.)
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Participation ended

Germany
EU contribution
€ 877 481,11
Address
Hofgartenstrasse 8
80539 Munich
Activity type
Other
Administrative Contact
Antje Lemper-Rupp (Mrs.)