Journal Article

FZJ-2021-05901

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The intramolecular allostery of GRB2 governing its interaction with SOS1 is modulated by phosphotyrosine ligands

Kazemein Jasemi, N. S. ; Herrmann, C. ; Magdalena Estirado, E. ; Gremer, L.FZJ* ; Willbold, D.FZJ* ; Brunsveld, L. ; Dvorsky, R. (Corresponding author) ; Ahmadian, M. R. (Corresponding author)

2021
Portland Press London

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Please use a persistent id in citations: doi:10.1042/BCJ20210105

Abstract: Growth factor receptor-bound protein 2 (GRB2) is a trivalent adaptor protein and a key element in signal transduction. It interacts via its flanking nSH3 and cSH3 domains with the proline-rich domain (PRD) of the RAS activator SOS1 and via its central SH2 domain with phosphorylated tyrosine residues of receptor tyrosine kinases (RTKs; e.g. HER2). The elucidation of structural organization and mechanistic insights into GRB2 interactions, however, remain challenging due to their inherent flexibility. This study represents an important advance in our mechanistic understanding of how GRB2 links RTKs to SOS1. Accordingly, it can be proposed that (1) HER2 pYP-bound SH2 potentiates GRB2 SH3 domain interactions with SOS1 (an allosteric mechanism); (2) the SH2 domain blocks cSH3, enabling nSH3 to bind SOS1 first before cSH3 follows (an avidity-based mechanism); and (3) the allosteric behavior of cSH3 to other domains appears to be unidirectional, although there is an allosteric effect between the SH2 and SH3 domains.

Note: Kein Post-print vorhanden

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Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5244 - Information Processing in Neuronal Networks (POF4-524) (POF4-524)

Appears in the scientific report 2021

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Database coverage:
; Allianz-Lizenz / DFG ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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