Role of salt bridges in the dimer interface of 14-3-3zeta in dimer dynamics, N-terminal alpha-helical order, and molecular chaperone activity
Publication Year 2018-01-05,Volume 293,Issue #1,Page 89-99
Journal Title
Journal of Biological Chemistry
Publication Type
Journal Article
The 14-3-3 family of intracellular proteins are dimeric, multifunctional 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 14-3-3zeta. 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 N-terminal helices of 14-3-3zeta, suggesting that this residue plays an important role in maintaining structure across the dimer interface. Intriguingly, a D21N 14-3-3zeta mutant exhibited enhanced molecular chaperone ability that prevented amorphous protein aggregation, suggesting a potential role for N-terminal disorder in 14-3-3zeta's poorly understood chaperone action. Taken together, these results imply that disorder in the N-terminal helices of 14-3-3zeta is a consequence of the dimer-monomer dynamics and may play a role in conferring chaperone function to 14-3-3zeta protein.
WEHI Research Division(s)
Systems Biology And Personalised Medicine
PubMed ID
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Creation Date: 2018-02-14 04:25:24
Last Modified: 2019-06-17 03:05:36
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