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Chem Biol. 2015 Jun 18;22(6):776-84. doi: 10.1016/j.chembiol.2015.05.008.

Growth Factor Identity Is Encoded by Discrete Coiled-Coil Rotamers in the EGFR Juxtamembrane Region.

Author information

1
Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520-8107, USA.
2
Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520-8107, USA; Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA. Electronic address: alanna.schepartz@yale.edu.

Abstract

Binding of transforming growth factor α (TGF-α) to the epidermal growth factor receptor (EGFR) extracellular domain is encoded through the formation of a unique antiparallel coiled coil within the juxtamembrane segment. This new coiled coil is an "inside-out" version of the coiled coil formed in the presence of epidermal growth factor (EGF). A third, intermediary coiled-coil interface is formed in the juxtamembrane region when EGFR is stimulated with betacellulin. The seven growth factors that activate EGFR in mammalian systems (EGF, TGF-α, epigen, epiregulin, betacellulin, heparin-binding EGF, and amphiregulin) fall into distinct categories in which the structure of the coiled coil induced within the juxtamembrane region correlates with cell state. The observation that coiled-coil state tracks with the downstream signaling profiles for each ligand provides evidence for growth factor functional selectivity by EGFR. Encoding growth factor identity in alternative coiled-coil rotamers provides a simple and elegant method for communicating chemical information across the plasma membrane.

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PMID:
26091170
PMCID:
PMC4487654
DOI:
10.1016/j.chembiol.2015.05.008
[Indexed for MEDLINE]
Free PMC Article

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