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|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|
|Citation:||Journal of Biological Chemistry, 2018; 293(1):89-99|
|Publisher:||American Society for Biochemistry and Molecular Biology|
|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.|
|Appears in Collections:||Chemistry publications|
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