Mechanism of Allosteric Coupling into and through the Plasma Membrane by EGFR.
Cell Chem Biol
; 25(7): 857-870.e7, 2018 07 19.
Article
in En
| MEDLINE
| ID: mdl-29731426
ABSTRACT
Epidermal growth factor receptor (EGFR) interacts through its extracellular domain with seven different growth factors. These factors induce different structures within the cytoplasmic juxtamembrane (JM) segment of the dimeric receptor and propagate different growth factor-dependent signals to the cell interior. How this process occurs is unknown. Here we apply diverse experimental and computational tools to show that growth factor identity is encoded by the EGFR transmembrane (TM) helix into discrete helix dimer populations that differ in both cross-location and cross-angle. Helix dimers with smaller cross-angles at multiple cross locations are decoded to induce an EGF-type coiled coil in the adjacent JM, whereas helix dimers with larger cross-angles at fewer cross locations induce the TGF-α-type coiled coil. We propose an updated model for how conformational coupling across multiple EGFR domains results in growth factor-specific information transfer, and demonstrate that this model applies to both EGFR and the related receptor ErbB2.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Membrane
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Cell Chem Biol
Year:
2018
Document type:
Article
Affiliation country:
United States