Hidden disorder propensity of the N-terminal segment of universal adapter protein 14-3-3 is manifested in its monomeric form: Novel insights into protein dimerization and multifunctionality

Biochimica Et Biophysica Acta
Nikolai N Sluchanko, Vladimir N Uversky

Abstract

The multiplicity of functions of 14-3-3 proteins, integrated into many cellular interactions and signaling networks, is primarily based upon their dimeric α-helical structure that is capable of binding phosphorylated protein partners as well as displaying a "moonlighting" chaperone-like activity. The structure and functions of 14-3-3 proteins are regulated in different ways, including Ser58 phosphorylation in the interface, which shifts equilibrium towards the formation of protein monomers whose role is poorly understood. While modification of Ser58 induced only partial dissociation, the engineered triple mutation of human 14-3-3ζ located in the first α-helix deeply monomerized the protein, allowing for a structural analysis of the monomeric form. Dimer-incapable 14-3-3 proteins retained binding capacity and specificity towards some phosphopartners, and also demonstrated increased chaperone-like activity on various substrates. Here, we found a substantial propensity of the N-terminal segment (~40 residues) of 14-3-3 proteins to intrinsic disorder, showing remarkable conservation across different isoforms and organisms. We hypothesized that this intrinsic disorder propensity, hidden in the α-helical 14-3-3 dimer, can be manifest...Continue Reading

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Citations

May 10, 2016·Biochimica Et Biophysica Acta. General Subjects·Zehra SayersInes Karmous
Dec 16, 2016·The FEBS Journal·Nikolai N Sluchanko, Nikolai B Gusev
Sep 27, 2018·Nature Communications·Nikolai N SluchankoEugene G Maksimov
Oct 20, 2019·Scientific Reports·Kristina V TugaevaNikolai N Sluchanko
Sep 22, 2017·Scientific Reports·Nikolai N SluchankoAlfred A Antson
Feb 9, 2021·Journal of Molecular Biology·Kristina V TugaevaNikolai N Sluchanko
Sep 23, 2021·NPJ Parkinson's Disease·E GiustoL Civiero

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