The A391E mutation enhances FGFR3 activation in the absence of ligand

Fenghao Chen, Catherine Degnin, Melanie Laederich, William A. Horton, Kalina A Hristova

Research output: Contribution to journalArticle

Abstract

The A391E mutation in the transmembrane domain of fibroblast growth factor receptor 3 leads to aberrant development of the cranium. It has been hypothesized that the mutant glutamic acid stabilizes the dimeric receptor due to hydrogen bonding and enhances its ligand-independent activation. We previously tested this hypothesis in lipid bilayers and showed that the mutation stabilizes the isolated transmembrane domain dimer by - 1.3 ° kcal/mol. Here we further test the hypothesis, by investigating the effect of the A391E mutation on the activation of full-length fibroblast growth factor receptor 3 in Human Embryonic Kidney 293T cells in the absence of ligand. We find that the mutation enhances the ligand-independent activation propensity of the receptor by - 1.7 ° kcal/mol. This value is consistent with the observed strength of hydrogen bonds in membranes, and supports the above hypothesis.

Original languageEnglish (US)
Pages (from-to)2045-2050
Number of pages6
JournalBBA - Biomembranes
Volume1808
Issue number8
DOIs
StatePublished - Aug 2011

Fingerprint

Receptor, Fibroblast Growth Factor, Type 3
Chemical activation
Ligands
Mutation
Hydrogen bonds
Lipid bilayers
Dimers
Glutamic Acid
HEK293 Cells
Lipid Bilayers
Hydrogen Bonding
Skull
Membranes
Hydrogen
Kidney

Keywords

  • Cell signaling
  • Membrane proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biophysics

Cite this

The A391E mutation enhances FGFR3 activation in the absence of ligand. / Chen, Fenghao; Degnin, Catherine; Laederich, Melanie; Horton, William A.; Hristova, Kalina A.

In: BBA - Biomembranes, Vol. 1808, No. 8, 08.2011, p. 2045-2050.

Research output: Contribution to journalArticle

Chen, Fenghao ; Degnin, Catherine ; Laederich, Melanie ; Horton, William A. ; Hristova, Kalina A. / The A391E mutation enhances FGFR3 activation in the absence of ligand. In: BBA - Biomembranes. 2011 ; Vol. 1808, No. 8. pp. 2045-2050.
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