title: Bringing dynamic molecular machines into focus by methyl-TROSY NMR.
abstract: Large macromolecular assemblies, so-called molecular machines, are critical to ensuring proper cellular function. Understanding how proper function is achieved at the atomic level is crucial to advancing multiple avenues of biomedical research. Biophysical studies often include X-ray diffraction and cryo-electron microscopy, providing detailed structural descriptions of these machines. However, their inherent flexibility has complicated an understanding of the relation between structure and function. Solution NMR spectroscopy is well suited to the study of such dynamic complexes, and continued developments have increased size boundaries; insights into function have been obtained for complexes with masses as large as 1 MDa. We highlight methyl-TROSY (transverse relaxation optimized spectroscopy) NMR, which enables the study of such large systems, and include examples of applications to several cellular machines. We show how this emerging technique contributes to an understanding of cellular function and the role of molecular plasticity in regulating an array of biochemical activities.
authors.affiliation: Departments of 1Biochemistry and.
authors.forename: Rina
authors.initials: R
authors.lastname: Rosenzweig
authors.forename: Lewis E
authors.initials: LE
authors.lastname: Kay
mesh_terms: D000495:Allosteric Site; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D020134:Catalytic Domain; D055354:Exosomes; D024242:HMGN2 Protein / Q000737:chemistry; D006360:Heat-Shock Proteins / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D046911:Macromolecular Substances / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D009707:Nucleosomes / Q000737:chemistry; D015221:Potassium Channels / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D024242:HMGN2 Protein; D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D009707:Nucleosomes; D015221:Potassium Channels; D011506:Proteins; C107790:prokaryotic potassium channel; D046988:Proteasome Endopeptidase Complex
keywords: allostery; deuteration; high–molecular weight complexes; methyl labeling; protein NMR; protein–substrate interactions