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

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.

  • remco sprangers fig-01
    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.

 


Available PhD Projects

No projects offered in the 2017 selection.

Selected Reading

1) Wiesner S, Sprangers R. Methyl groups as NMR probes for biomolecular interactions. (2015) Curr Opin Struct Biol. 35, 60-67.

2) Neu A, Neu U, Fuchs AL, Schlager B, Sprangers R. (2015) An excess of catalytically required motions inhibits the scavenger decapping enzyme. Nat Chem Biol. 11(9), 697-704.

3) Mund M, Overbeck JH, Ullmann J, Sprangers R. (2013) LEGO-NMR spectroscopy: a method to visualize individual subunits in large heteromeric complexes. Angew Chem Int Ed Engl., 52, 11401-5.