Dataset Information

Internal Motions of Basic Side Chains of the Antennapedia Homeodomain in the Free and DNA-Bound States.

ABSTRACT: Basic side chains play crucial roles in protein-DNA interactions. In this study, using NMR spectroscopy, we investigated the dynamics of Arg and Lys side chains of the fruit fly Antennapedia homeodomain in the free state and in the complex with target DNA. We measured 15N relaxation for Arg and Lys side chains at two magnetic fields, from which generalized order parameters for the cationic groups were determined. Mobility of the R5 side chain, which makes hydrogen bonds with a thymine base in the DNA minor groove, was greatly dampened. Several Lys and Arg side chains that form intermolecular ion pairs with DNA phosphates were found to retain high mobility with the order parameter being <0.6 in the DNA-bound state. Interestingly, some of the interfacial cationic groups in the complex were more mobile than in the free protein. The retained or enhanced mobility of the Arg and Lys side chains in the complex should mitigate the overall loss of conformational entropy in the protein-DNA association and allow dynamic molecular recognition.

SUBMITTER: Nguyen D

PROVIDER: S-EPMC5682595 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Internal Motions of Basic Side Chains of the Antennapedia Homeodomain in the Free and DNA-Bound States.

Nguyen Dan D Hoffpauir Zoe A ZA Iwahara Junji J

Biochemistry 20171101 44

Basic side chains play crucial roles in protein-DNA interactions. In this study, using NMR spectroscopy, we investigated the dynamics of Arg and Lys side chains of the fruit fly Antennapedia homeodomain in the free state and in the complex with target DNA. We measured <sup>15</sup>N relaxation for Arg and Lys side chains at two magnetic fields, from which generalized order parameters for the cationic groups were determined. Mobility of the R5 side chain, which makes hydrogen bonds with a thymine ...[more]

PMID: 29045141

Similar Datasets

Project description:Protein interactions play a key role in life processes. Characterization of conformational properties of protein-protein interactions is important for understanding the mechanisms of protein association. The rapidly increasing amount of experimentally determined structures of proteins and protein-protein complexes provides foundation for research on protein interactions and complex formation. The knowledge of the conformations of the surface side chains is essential for modeling of protein complexes. The purpose of this study was to analyze and compare dihedral angle distribution functions of the side chains at the interface and non-interface areas in bound and unbound proteins.To calculate the dihedral angle distribution functions, the configuration space was divided into grid cells. Statistical analysis showed that the similarity between bound and unbound interface and non-interface surface depends on the amino acid type and the grid resolution. The correlation coefficients between the distribution functions increased with the grid spacing increase for all amino acid types. The Manhattan distance showing the degree of dissimilarity between the distribution functions decreased accordingly. Short residues with one or two dihedral angles had higher correlations and smaller Manhattan distances than the longer residues. Met and Arg had the slowest growth of the correlation coefficient with the grid spacing increase. The correlations between the interface and non-interface distribution functions had a similar dependence on the grid resolution in both bound and unbound states. The interface and non-interface differences between bound and unbound distribution functions, caused by biological protein-protein interactions or crystal contacts, disappeared at the 70° grid spacing for interfaces and 30° for non-interface surface, which agrees with an average span of the side-chain rotamers.The two-fold difference in the critical grid spacing indicates larger conformational changes upon binding at the interface than at the rest of the surface. At the same time, transitions between rotamers induced by interactions across the interface or the crystal packing are rare, with most side chains having local readjustments that do not change the rotameric state. The analysis is important for better understanding of protein interactions and development of flexible docking approaches.

Dataset Information

Internal Motions of Basic Side Chains of the Antennapedia Homeodomain in the Free and DNA-Bound States.

Publications

Internal Motions of Basic Side Chains of the Antennapedia Homeodomain in the Free and DNA-Bound States.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets