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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
Statement of
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
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
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Appears in Collections:Aurora harvest 3
Chemistry publications

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