Nuclear magnetic resonance (NMR) studies carried out in the 1970s surprisingly demonstrated that aromatic amino acids in proteins can undergo ring rotations (or so-called flips). Paradoxically, these aromatic amino acids are in many cases located in the tightly-packed protein core, where they engage in multiple interactions to maintain the protein fold and thereby function. At that time, it was proposed that large-scale protein “breathing motions” would be necessary in order to accommodate these ring rotations, however, until now the structural details of these motions have remained elusive.
By combining NMR spectroscopy and X-ray crystallography, researchers at the IBS (Protein Dynamics and Flexibility by NMR group) in collaboration with researchers at the IAB (Palencia’s group) have revealed for the first time the structural changes associated with aromatic ring rotations in the core of a protein. The study shows how a void volume is generated around the aromatic ring to allow the ring rotation to occur.
This discovery, published in Nature on february 16, has implications for both protein design and structure prediction by highlighting how even small alterations in the delicate balance of interactions stabilizing the core can lead to major changes in the protein structure.
Visualizing protein breathing motions associated with aromatic ring flipping. L. Mariño Pérez, F.S. Ielasi, L.M. Bessa, D. Maurin, J. Kragelj, M. Blackledge, N. Salvi, G. Bouvignies, A. Palencia*, M.R. Jensen*. Nature (2022). https://doi.org/10.1038/s41586-022-04417-6
Contact : Malene R. Jensen (IBS/Group Protein Dynamics and Flexibility by NMR)