The achondroplasia mutation does not alter the dimerization energetics of the fibroblast growth factor receptor 3 transmembrane domain

Min You, Edwin Li, Kalina A Hristova

Research output: Contribution to journalArticle

Abstract

The Gly380 → Arg mutation in the TM domain of fibroblast growth factor receptor 3 (FGFR3) of the RTK family is linked to achondroplasia, the most common form of human dwarfism. The molecular mechanism of pathology induction is under debate, and two different mechanisms have been proposed to contribute to pathogenesis: (1) Arg380-mediated FGFR3 dimer stabilization and (2) slow downregulation of the activated mutant receptors. Here we show that the Gly380 → Arg mutation does not alter the dimerization energetics of the FGFR3 transmembrane domain in detergent micelles or in lipid bilayers. This result indicates that pathogenesis in achondroplasia cannot be explained simply by a higher dimerization propensity of the mutant FGFR3 TM domain, thus highlighting the importance of the observed slow downregulation in phenotype induction.

Original languageEnglish (US)
Pages (from-to)5551-5556
Number of pages6
JournalBiochemistry®
Volume45
Issue number17
DOIs
StatePublished - May 2 2006

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Receptor, Fibroblast Growth Factor, Type 3
Achondroplasia
Dimerization
Mutation
Down-Regulation
Dwarfism
Lipid bilayers
Molecular Pathology
Lipid Bilayers
Micelles
Pathology
Detergents
Dimers
Stabilization
Phenotype

ASJC Scopus subject areas

  • Biochemistry

Cite this

The achondroplasia mutation does not alter the dimerization energetics of the fibroblast growth factor receptor 3 transmembrane domain. / You, Min; Li, Edwin; Hristova, Kalina A.

In: Biochemistry®, Vol. 45, No. 17, 02.05.2006, p. 5551-5556.

Research output: Contribution to journalArticle

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