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

Biochemistry
Min YouKalina Hristova

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.

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Citations

Jun 15, 2007·The Journal of Membrane Biology·Mikhail MerzlyakovKalina Hristova
Jul 16, 2009·The Journal of Membrane Biology·Ricky SoongKalina Hristova
Jun 4, 2013·The Journal of Membrane Biology·Krishna C MudumbiEdwin Li
May 9, 2012·Expert Reviews in Molecular Medicine·Melanie B Laederich, William A Horton
Sep 8, 2011·Biochemistry·Fenghao Chen, Kalina Hristova
May 18, 2013·Journal of the American Chemical Society·Pavel E VolynskyRoman G Efremov
Jul 14, 2010·The Journal of Biological Chemistry·Lijuan HeKalina Hristova
Feb 18, 2011·The Journal of Biological Chemistry·Lijuan HeKalina Hristova
Jul 6, 2010·Current Opinion in Pediatrics·Melanie B Laederich, William A Horton
Jul 20, 2011·Journal of Molecular Biology·Lijuan HeWilliam C Wimley
Mar 24, 2009·Journal of Structural Biology·Edwin LiKalina Hristova
Jul 17, 2007·Lancet·William A HortonJacqueline T Hecht
Jun 9, 2007·Journal of Molecular Biology·Ann Marie Stanley, Karen G Fleming
Jun 17, 2009·Protein Science : a Publication of the Protein Society·Dieter Langosch, Isaiah T Arkin
Dec 25, 2009·American Journal of Medical Genetics. Part a·María Luisa Martínez-FríasUNKNOWN ECEMC Working Group
Aug 16, 2011·Biochimica Et Biophysica Acta·Lijuan He, Kalina Hristova
Sep 14, 2011·Biochimica Et Biophysica Acta·Edwin LiKalina Hristova
Jul 5, 2013·Biophysical Journal·Sarvenaz Sarabipour, Kalina Hristova
Nov 4, 2008·Journal of Molecular Biology·Lijuan He, Kalina Hristova
Jun 3, 2009·Biophysical Journal·Lirong ChenKalina Hristova
Nov 14, 2017·PloS One·Matti JavanainenIlpo Vattulainen
Jun 8, 2007·Orthodontics & Craniofacial Research·Machael L CunninghamAnne V Hing
Dec 28, 2019·The Journal of Biological Chemistry·Justin M Westerfield, Francisco N Barrera
Mar 16, 2021·Journal of Chemical Theory and Computation·Ayan Majumder, John E Straub

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