Transmembrane helix heterodimerization in lipid bilayers: probing the energetics behind autosomal dominant growth disorders.
Here, we show that the energetics of transmembrane helix heterodimer formation can be characterized in liposomes using Förster resonance energy transfer (FRET). We present the theory and the protocol for measuring the free energy of heterodimerization, and the total (hetero and homo-dimeric) dimer fraction. We use the presented methodology to determine the propensity for heterodimer formation between wild-type fibroblast growth factor receptor 3 (FGFR3) transmembrane domain and the Ala391Glu mutant, linked to Crouzon syndrome with acanthosis nigricans.
Merzlyakov
Mikhail
M
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore MD 21218, USA.
You
Min
M
Li
Edwin
E
Hristova
Kalina
K
D000052:Acanthosis Nigricans / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D003394:Craniofacial Dysostosis / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D031541:Fluorescence Resonance Energy Transfer; D005799:Genes, Dominant / Q000235:genetics*; D006130:Growth Disorders / Q000235:genetics* / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
D008051:Lipid Bilayers; D008565:Membrane Proteins; D051498:Receptor, Fibroblast Growth Factor, Type 3