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https://hdl.handle.net/2440/114079
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Type: | Journal article |
Title: | Role of salt bridges in the dimer interface of 14-3-3ζ in dimer dynamics, N-terminal α-helical order, and molecular chaperone activity |
Other Titles: | Role of salt bridges in the dimer interface of 14-3-3zeta in dimer dynamics, N-terminal alpha-helical order, and molecular chaperone activity |
Author: | Woodcock, J. Goodwin, K. Sandow, J. Coolen, C. Perugini, M. Webb, A. Pitson, S. Lopez, A. Carver, J. |
Citation: | Journal of Biological Chemistry, 2018; 293(1):89-99 |
Publisher: | American Society for Biochemistry and Molecular Biology |
Issue Date: | 2018 |
ISSN: | 0021-9258 1083-351X |
Statement of Responsibility: | Joanna M. Woodcock, Katy L. Goodwin, Jarrod J. Sandow, Carl Coolen, Matthew A. Perugini, Andrew I. Webb, Stuart M. Pitson, Angel F. Lopez and John A. Carver |
Abstract: | The 14-3-3 family of intracellular proteins are dimeric, multi-functional adaptor proteins that bind to and regulate the activities of many important signaling proteins. The subunits within 14-3-3 dimers are predicted to be stabilized by salt bridges that are largely conserved across the 14-3-3 protein family and allow the different isoforms to form heterodimers. Here, we have examined the contributions of conserved salt-bridging residues in stabilizing the dimeric state of 14-3-3ζ. Using analytical ultracentrifugation, our results revealed that Asp-21 and Glu-89 both play key roles in dimer dynamics and contribute to dimer stability. Furthermore, hydrogen-deuterium exchange coupled with mass spectrometry showed that mutation of Asp-21 promoted disorder in the amino-terminal helices of 14-3-3ζ, suggesting that this residue plays an important role in maintaining structure across the dimer interface. Intriguingly, a D21N 14-3-3ζ mutant exhibited enhanced molecular chaperone ability that prevented amorphous protein aggregation, suggesting a potential role for N-terminal disorder in 14-3-3ζ's poorly understood chaperone action. Taken together, these results imply that disorder in the N-terminal helices of 14-3-3ζ is a consequence of the dimer monomer dynamics and may play a role in conferring chaperone function to 14-3-3ζ protein. |
Keywords: | 14-3-3 protein analytical ultracentrifugation dimer interface dimerization hydrogen-deuterium exchange molecular chaperone protein conformation protein disorder salt bridge |
Rights: | © 2018 by The American Society for Biochemistry and Molecular Biology, Inc. |
DOI: | 10.1074/jbc.M117.801019 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1068087 http://purl.org/au-research/grants/nhmrc/1042589 |
Published version: | http://dx.doi.org/10.1074/jbc.m117.801019 |
Appears in Collections: | Aurora harvest 3 Chemistry publications |
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