Backbone chemical shift assignments of human 14-3-3$\sigma$

TL;DR

This paper reports the backbone chemical shift assignments of the human 14-3-3σ isoform, providing essential NMR data to facilitate drug discovery targeting this protein's interactions.

Contribution

The study provides the first robust backbone NMR assignments for human 14-3-3σ, enabling further biological and chemical biology research.

Findings

Backbone assignments achieved for 14-3-3σ isoform.

Data supports development of inhibitors and stabilizers.

Facilitates studies on isoform-specific functions.

Abstract

14-3-3 proteins are a group of seven dimeric adapter proteins that exert their biological function by interacting with hundreds of phosphorylated proteins, thus influencing their sub-cellular localization, activity or stability in the cell. Due to this remarkable interaction network, 14-3-3 proteins have been associated with several pathologies and the protein-protein interactions established with a number of partners are now considered promising drug targets. The activity of 14-3-3 proteins is often isoform specific and to our knowledge only one out of seven isoforms, 14-3-3$\zeta$, has been assigned. Despite the availability of the crystal structures of all seven isoforms of 14-3-3, the additional NMR assignments of 14-3-3 proteins are important for both biological mechanism studies and chemical biology approaches. Herein, we present a robust backbone assignment of 14-3-3$\sigma$, which will allow advances in the discovery of potential therapeutic compounds. This assignment is now being applied to the discovery of both inhibitors and stabilizers of 14-3-3 protein-protein interactions.