The A391E mutation enhances FGFR3 activation in the absence of ligand

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

Research output: Contribution to journalArticlepeer-review

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
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1808
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • Cell signaling
  • Membrane proteins

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'The A391E mutation enhances FGFR3 activation in the absence of ligand'. Together they form a unique fingerprint.

Cite this