Abstract
Proteins in cells or cell membranes at physiological temperature are highly dynamic systems characterized by “elemental rate processes” in the nanosecond to picosecond frequency range. Additional low-frequency large-amplitude motions have been detected by NMR (nuclear magnetic resonance) observation of tyrosine and phenylalanine 180-degree “ring flips” [1] (this reference includes a short historical survey). Ring flips are observable by NMR because of the absence of periodicity in the distribution of atom groups across the interior of folded proteins, which results in non-uniform magnetic microsusceptibility experienced by pairs of chemically identical, symmetry-related ring substituents. Exchange of aromatic ring substituents by 180-degree rotational flipping motions about the single bond by which the ring is attached to the polypeptide chain connects two non-distinguishable conformational states of the rings. These rate processes affect the line shapes of the NMR signals, and they can also be observed by two-dimensional exchange spectroscopy. In soluble proteins, flipping of phenylalanine and tyrosine rings has been observed at frequencies from about 1 s-1 to 108 s-1, manifesting transient structure fluctuations with an amplitude of about 1.5 Å [1]. For flipping motions of trifluoromethyl-substituted aromatic rings, the corresponding amplitude is 6 to 8 Å. Such large structure fluctuations have been observed in G protein-coupled receptors (GPCR) [2]; implications of this observation on the mechanism of action of GPCRs will be discussed.
