title: NMR analysis of dynein light chain dimerization and interactions with diverse ligands.
abstract: NMR is a powerful tool for quantitative measurement of the thermodynamic properties of biological systems. In this review, we discuss the role NMR has played in understanding the various coupled equilibria in dimerization of dynein light chain LC8 and in its interactions with its ligands. LC8, a very highly conserved 89-residue homodimer also known as DYNLL, is an essential component of the dynein and Myosin V molecular motors and is also found in various other complexes. LC8 binds to disordered segments of its partners, promoting them to dimerize and form more ordered structures, often coiled coils. The monomer-dimer equilibrium is controlled by electrostatic interactions at the dimer interface, such as by phosphorylation of residue Ser88, which is a regulatory mechanism for LC8 in vivo. NMR experiments have uncovered several subtle interactions--weak dimerization of a phosphomimetic mutant, and allosteric interaction between the LC8 binding sites--that have been overlooked by other methods. NMR has also provided a residue-specific view of the titration of histidine residues at the LC8 dimer interface, and of a nascent helix in one of the binding partners, the primarily disordered dynein intermediate chain IC74. We give special attention to methods for quantitative interpretation of NMR spectra, an important consideration when using NMR to measure equilibria.
authors.affiliation: Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Benison
authors.forename: Elisar
authors.initials: E
authors.lastname: Barbar
mesh_terms: D000495:Allosteric Site; D004398:Dyneins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D017510:Protein Folding; D055503:Protein Multimerization; D055672:Static Electricity
chemical_list: D008024:Ligands; D004398:Dyneins