Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.09.290122v1?rss=1 Authors: Pinet, L., Wang, Y., Deville, C., Lescop, E., Badache, A., Bontems, F., Morellet, N., Durand, D., Guerlesquin, F., Assrir, N., van Heijenoort, C. Abstract: ErbB2 (or HER2) is a receptor tyrosine kinase overexpressed in some breast cancers, associated with poor prognosis. Treatments targeting the receptor extracellular and kinase domains have greatly improved disease outcome in the last twenty years. In parallel, the structures of these domains have been described, enabling better mechanistic understanding of the receptor function and targeted inhibition. However, ErbB2 disordered C-terminal cytoplasmic tail (CtErbB2) remains very poorly characterized in terms of structure, dynamics and detailed functional mechanism. Yet, it is where signal transduction is triggered, via phosphorylation of tyrosine residues, and carried out, via interaction with adaptor proteins. Here we report the first description of ErbB2 disordered tail at atomic resolution, using NMR and SAXS. We show that although no part of CtErbB2 has any stable secondary or tertiary structure, it has around 20% propensity for a N-terminal helix that is suspected to interact with the kinase domain, and many PPII stretches distributed all along the sequence, forming potential SH3 and WW domains binding sites. Moreover, we identified a long-range transient contact involving CtErbB2 termini. These characteristics suggest new potential mechanisms of auto-regulation and protein-protein interaction. Copy rights belong to original authors. Visit the link for more info