Skip to Main content Skip to Navigation
Journal articles

Structural and dynamic characterization of the C-terminal tail of ErbB2: disordered but not random

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, complemented by SAXS. We show that although no part of CtErbB2 has any fully populated secondary or tertiary structure, it contains several transient helices and numerous transient PPII helices, populated up to 20 and 40% respectively, and low but significant compaction. The presence of some structural elements suggests, along the lines of the results obtained for EGFR (ErbB1), that they may have a functional role in ErbB2’s auto-regulation processes. In addition, the transient formation of PPII helices is compliant with previously suggested interactions with SH3 domains. All in all, our in-depth structural study opens new perspectives in the mechanistic understanding of ErbB2.
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-03095358
Contributor : Carine van Heijenoort Connect in order to contact the contributor
Submitted on : Friday, November 26, 2021 - 10:05:36 AM
Last modification on : Tuesday, January 25, 2022 - 3:11:59 AM

File

Pinet_BiophyJ_20210310.pdf
Files produced by the author(s)

Identifiers

Citation

L. Pinet, Y.-H. Wang, C. Deville, E. Lescop, F. Guerlesquin, et al.. Structural and dynamic characterization of the C-terminal tail of ErbB2: disordered but not random. Biophysical Journal, Biophysical Society, 2021, 120 (10), pp.1869-1882. ⟨10.1016/j.bpj.2021.03.005⟩. ⟨hal-03095358v2⟩

Share

Metrics

Les métriques sont temporairement indisponibles