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.