Journal Article

FZJ-2019-05668

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Molecular Architecture of a Network of Potential Intracellular EGFR Modulators Involving the Juxtamembrane Segment, ARNO, Phospholipids and CaM

Viegas, A. ; Yin, D. M. ; Borggräfe, J. ; Viennet, T. ; Falke, M. ; Schmitz, A. ; Famulok, M. ; Etzkorn, M. (Corresponding author)FZJ*

2020
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: http://hdl.handle.net/2128/24668  doi:10.2139/ssrn.3441425

Abstract: Signaling of the Epidermal growth factor receptors (EGFRs) is a central cellular element and its dysregulation is related to a number of severe diseases. While ligand binding to the extracellular domain is the receptor’s most obvious regulatory element, also intracellular factors can act as modulators of EGFR activity. The juxtamembrane (JM) segment of the EGFR seems to be a key interaction interface of these cytoplasmic factors. However, very few JM-interacting molecules have been identified so far and even fewer is known about the molecular mechanism underlying JM-targeted receptor modulation. Here we report ARNO as a new EGFR-JM binding protein and provide high-resolution insights into its mode of interaction. We obtain comparable insights also for the known interaction partners Calmodulin and phospholipid bilayers containing different lipid compositions. Our results show clear similarities and distinct differences in each binding mode. Furthermore, we show that each interaction can be modulated by a set of additional orthogonal factors generating a distinctly regulated competitive network of possible EGFR modulators acting on the intracellular domain of the receptor. This newly identified interaction network and the obtained insights into the underlaying molecular mechanism may foster future EGFR-targeted therapeutic strategies.

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Contributing Institute(s):

1. Strukturbiochemie (ICS-6)

Research Program(s):

1. 552 - Engineering Cell Function (POF3-552) (POF3-552)

Appears in the scientific report 2020

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Database coverage:
; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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