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 language | English (US) |
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Pages (from-to) | 2045-2050 |
Number of pages | 6 |
Journal | Biochimica et Biophysica Acta - Biomembranes |
Volume | 1808 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2011 |
Keywords
- Cell signaling
- Membrane proteins
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Cell Biology