Molecular Architecture of a Network of Potential Intracellular EGFR Modulators: ARNO, CaM, Phospholipids, and the Juxtamembrane Segment.
Structure
; 28(1): 54-62.e5, 2020 01 07.
Article
en En
| MEDLINE
| ID: mdl-31780432
ABSTRACT
Epidermal growth factor receptors (EGFRs) are central cellular signaling interfaces whose misregulation is related to several severe diseases. Although ligand binding to the extracellular domain is the most obvious regulatory element, also intracellular factors can act as modulators of EGFR activity. The juxtamembrane (JM) segment seems to be the receptor's key interaction interface of these cytoplasmic factors. However, only a limited number of cytoplasmic EGFR modulators are known and a comprehensive understanding of their mode of action is lacking. Here, we report ARNO, a member of the cytohesin family, as another JM-binding protein and structurally characterize the ARNO-EGFR interaction interface. We reveal that its binding mode displays common features and distinct differences with JM's interaction with calmodulin and anionic phospholipids. Furthermore, we show that each interaction can be modulated by additional factors, generating a distinctly regulated network of possible EGFR modulators acting on the intracellular domain of the receptor.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fosfolípidos
/
Calmodulina
/
Proteínas Activadoras de GTPasa
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Structure
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania