Structures of Large Protein Complexes Determined by Nuclear Magnetic Resonance Spectroscopy

Abstract

Nuclear magnetic resonance (NMR) spectroscopy has been instrumental during the past two decades in providing high-resolution structures of protein complexes. It has been the method of choice for determining the structure of dynamic protein complexes, which are typically recalcitrant to other structural techniques. Until recently, NMR spectroscopy has yielded structures of small or medium-sized protein complexes, up to approximately 30–40 kDa. Major breakthroughs during the past decade, especially in isotope-labeling techniques, have enabled NMR characterization of large protein systems with molecular weights of hundreds of kDa. This has provided unique insights into the binding, dynamic, and allosteric properties of large systems. Notably, there is now a slowly but steadily growing list of large, dynamic protein complexes whose atomic structure has been determined by NMR. Many of these complexes are characterized by a high degree of flexibility and, thus, their structures could not have been obtained using other structural methods. Especially in the field of molecular chaperones, NMR has recently provided the first-ever high-resolution structures of their complexes with unfolded proteins. Further technological advances will establish NMR as the primary tool for obtaining atomic structures of challenging systems with even higher complexity.