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Growth factor identity is encoded by discrete coiled coil rotamers in the EGFR juxtamembrane region
- Source :
- Chemistry & biology, vol 22, iss 6
- Publication Year :
- 2015
-
Abstract
- SummaryBinding 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.
- Subjects :
- TGF alpha
Clinical Biochemistry
Biochemistry
Epiregulin
0302 clinical medicine
Epidermal growth factor
Cricetinae
Drug Discovery
Epidermal growth factor receptor
Coiled coil
Microscopy
0303 health sciences
General Medicine
Cell biology
Molecular Docking Simulation
ErbB Receptors
Epigen
030220 oncology & carcinogenesis
Molecular Medicine
Intercellular Signaling Peptides and Proteins
Signal Transduction
Protein Structure
1.1 Normal biological development and functioning
Molecular Sequence Data
CHO Cells
Biology
Fluorescence
Article
Medicinal and Biomolecular Chemistry
03 medical and health sciences
Cricetulus
Amphiregulin
Underpinning research
Animals
Humans
Amino Acid Sequence
Betacellulin
Molecular Biology
030304 developmental biology
Pharmacology
Binding Sites
Epidermal Growth Factor
Organic Chemistry
Transforming Growth Factor alpha
Protein Structure, Tertiary
Microscopy, Fluorescence
Gene Expression Regulation
biology.protein
Generic health relevance
Biochemistry and Cell Biology
Tertiary
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Chemistry & biology, vol 22, iss 6
- Accession number :
- edsair.doi.dedup.....923a15065d9ec64fa8b704492fab3825