Measurement of 13Cα13Cβ Dipolar Couplings in 15N,13C,2H-Labeled Proteins: Application to Domain Orientation in Maltose Binding Protein

Abstract
TROSY-based HN(CO)CA 2D and 3D pulse schemes are presented for measurement of 13Cα13Cβ dipolar couplings in high molecular weight 15N,13C,2H-labeled proteins. In one approach, 13Cα13Cβ dipolar couplings are obtained directly from the time modulation of cross-peak intensities in a set of 2D 15N−1HN correlated spectra recorded in both the presence and absence of aligning media. In a second approach 3D data sets are recorded with 13Cα13Cβ couplings encoded in a frequency dimension. The utility of the experiments is demonstrated with an application to an 15N,13C,2H-labeled sample of the ligand free form of maltose binding protein. A comparison of experimental dipolar couplings with those predicted from the X-ray structure of the apo form of this two-domain protein establishes that the relative orientation of the domains in solution and in the crystal state are very similar. This is in contrast to the situation for maltose binding protein in complex with β-cyclodextrin where the solution structure can be generated from the crystal state via a 11° domain closure.

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