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NMR Spectroscopy of large complexes

Remco Sprangers

Remco Sprangers

  • PhD at the EMBL, Heidelberg, 1999-03
  • Postdoctoral training, University of Toronto, 2003-08
  • Max Planck research group leader at the MPI since 2008
  • 2017: moving to University of Regensburg

Research Interest

The primary scientific goal of the research group is to understand the relationship between protein motions and protein function. This is especially relevant for most enzymes, that have to undergo structural rearrangements to perform biological tasks. In the lab we focus on understanding the mechanism behind the bio-molecular complexes that play a role in the degradation of mRNA.

After export to the cytoplasm, mRNA is protected from degradation by a 5’ cap structure and a 3’ poly (A) tail. In the deadenylation dependent mRNA decay pathway, the poly(A) tail is gradually shortened by deadenylases. This ultimately attracts the machinery that rapidly degrades the mRNA. Additional mechanisms, including the nonsense mediated decay pathway, bypass the need for deadenylation and can remove the mRNA from the translational pool independently. Interestingly, the same enzymes are responsible for the actual degradation of the mRNA independently from the pathway taken.

Structural data for some of the isolated components of the mRNA decay machinery is known. Our understanding of enzyme function is, however, limited to a static 3-dimensional fold of one of the many conformations these proteins can adopt in isolation. To obtain a complete picture of how molecular motions and interactions regulate catalytic activity we exploit novel methods in Nuclear Magnetic Resonance (NMR) spectroscopy combined with X-ray crystallography, biochemical experiments and fluorescent microscopy.

Selected Reading

1) Sprangers R, Kay LE. (2007) Quantitative dynamics and binding studies of the 20S proteasome by NMR. Nature 445, 618-22.

2) Mund M, Neu A, Ullmann J, Neu U, Sprangers R. (2011) Structure of the LSm657 Complex: An Assembly Intermediate of the LSm1-7 and LSm2-8 Rings. J Mol Biol 414, 165-76.

3) Fromm SA, Truffault V, Kamenz J, Braun JE, Hoffmann NA, et al. (2011) The structural basis of Edc3- and Scd6-mediated activation of the Dcp1:Dcp2 mRNA decapping complex. EMBO J, published online November 15.
(click to enlarge)
Top: Crystal structure of the Lsm657 complex (PDB: 3SWN) and NMR spectra that report on the assembly process of the Lsm657 complex towards the Lsm1-7 and Lsm2-8 rings. Bottom: Solution structure (PDB: 4A54) and NMR spectra of the complex of Edc3 and Dcp2. The complex is important for the proper localization of the decapping machinery to P-bodies and for the activation of the activity of the Dcp1:Dcp2 decapping complex.