title: Coupling of transmembrane helix orientation to membrane release of the juxtamembrane region in FGFR3.
abstract: Activation of the protein tyrosine kinase receptors requires the coupling of ligand binding to a change in both the proximity and orientation of the single transmembrane (TM) helices of receptor monomers to allow transphosphorylation of the receptor kinase domain. We make use of peptides corresponding to the TM and juxtamembrane (JM) regions of the fibroblast growth factor receptor 3 to assess how mutations in the TM region (G380R and A391E), which lead to receptor activation, influence the orientation of the TM domain and interactions of the intracellular JM sequence with the membrane surface. On the basis of fluorescence and Fourier transform infrared spectroscopy, we find that both activating mutations change the TM helix tilt angle relative to the membrane normal and release the JM region from the membrane. These results suggest a general mechanism regarding how the TM-JM region functionally bridges the extracellular and intracellular regions for these receptors.
authors.affiliation: Institute for Protein Research, Osaka University , 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tamagaki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Hojo
authors.forename: Saburo
authors.initials: S
authors.lastname: Aimoto
authors.forename: Steven O
authors.initials: SO
authors.lastname: Smith
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sato
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D055503:Protein Multimerization / Q000502:physiology; D017433:Protein Structure, Secondary / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D051498:Receptor, Fibroblast Growth Factor, Type 3