Scientific reports, 2013-09, Vol.3 (1), p.2659-2659, Article 2659
2013
Details
- Autor(en) / Beteiligte
- Titel
- A disorder-to-order structural transition in the COOH-tail of Fz4 determines misfolding of the L501fsX533-Fz4 mutant
- Ist Teil von
- Scientific reports, 2013-09, Vol.3 (1), p.2659-2659, Article 2659
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Frizzled 4 belongs to the superfamily of G protein coupled receptors. The unstructured cytosolic tail of the receptor is essential for its activity. The mutation L501fsX533 in the fz4 gene results in a new COOH-tail of the receptor and causes a form of Familial exudative vitreoretinopathy. Here we show that the mutated tail is structured. Two amphipathic helices, displaying affinity for membranes and resembling the structure of Influenza Hemagglutinin fusion peptide, constitute the new fold. This tail induces the aggregation of the receptor in the Endoplasmic Reticulum and it is sufficient to block the export to the Golgi of a chimeric VSVG protein containing the mutated tail. Affecting the tail's structure, net charge or amphipathicity relocates the mutated Fz4 receptor to the Plasma Membrane. Such disorder-to-order structural transition was never described in GPCRs and opens a new scenario on the possible effect of mutations on unstructured regions of proteins.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/srep02659Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3773625
- Format
- –
- Schlagworte
- Amino Acid Sequence, Animals, Cell Line, Cell Membrane - metabolism, Endoplasmic reticulum, Endoplasmic Reticulum - metabolism, Familial Exudative Vitreoretinopathies, Familial exudative vitreoretinopathy, Frizzled protein, Frizzled Receptors - chemistry, Frizzled Receptors - genetics, Frizzled Receptors - metabolism, G protein-coupled receptors, Genetic Diseases, X-Linked - genetics, Golgi apparatus, Hemagglutinins, Humans, Influenza, Molecular Sequence Data, Mutation, Protein Binding, Protein Conformation, Protein Folding, Protein Interaction Domains and Motifs, Protein Structure, Secondary, Protein Transport, Rats, Recombinant Fusion Proteins - chemistry, Recombinant Fusion Proteins - metabolism, Sequence Alignment, Solutions, Vitreoretinopathy, Proliferative - genetics