Role of salt bridges in the dimer interface of 14-3-3ζ in dimer dynamics, N-terminal α-helical order and molecular chaperone activity

Journal: Journal of Biological Chemistry

Published: 2017-11-06

DOI: 10.1074/jbc.m117.801019

Affiliations: 6

Authors: 9

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Research Highlight

Bound by salt

© KATERYNA KON/SCIENCE PHOTO LIBRARY/Getty

© KATERYNA KON/SCIENCE PHOTO LIBRARY/Getty

A new study reveals how members of the 14-3-3 protein family chaperone their target proteins, including those linked with Alzheimer’s and Parkinson’s, such as tau proteins.

14-3-3 proteins become pairs to form dimers which are thought to be stabilized by salt bridges between sites in the two proteins. To understand the importance of these salt bridges, a team including researchers at the University of South Australia engineered a 14-3-3 protein in which the salt bridge-forming sites had been mutated.

The mutated proteins could not make salt bridges, but still formed dimers. These dimers, however, were more dynamic and thus less resilient to changes in temperature or concentration of 14-3-3 proteins. Further analysis revealed that the interface between the subunits of the dimer was more exposed in the mutated proteins, explaining the reduced dimer stability. Exposure of the interface in the mutated proteins also made them more effective at blocking the aggregation of signalling proteins.

Supported content

  1. Journal of Biological Chemistry 293, 89–99 (2018). doi: 10.1074/jbc.M117.801019
Institutions FC
Centre for Cancer Biology, Australia 0.44
School of Physical Sciences, Adelaide Uni, Australia 0.11
Division of Systems Biology and Personalised Medicine, WEHI, Australia 0.11
Department of Medical Biology, UniMelb, Australia 0.11
Department of Biochemistry and Genetics, La Trobe University, Australia 0.11
ANU Research School of Chemistry, Australia 0.11

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