Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1002/humu.9337
Titel (primär) Nephrogenic diabetes insipidus caused by mutation of Tyr205: A key residue of V2 vasopressin receptor function
Autor Sangkuhl, K.; Römpler, H.; Busch, W. ORCID logo ; Karges, B.; Schöneberg, T.
Quelle Human Mutation
Erscheinungsjahr 2005
Department ZELLTOX
Band/Volume 25
Heft 5
Seite von 505
Sprache englisch
Keywords V2 vasopressin receptor; nephrogenic diabetes insipidus; mutation; G-protein-coupled receptor
Abstract Mutations in the V2 vasopressin receptor (AVPR2) are the most frequent genetic cause of the inherited nephrogenic diabetes insipidus (NDI). About 50% of all missense mutations found in extracellular loops of AVPR2 introduce additional cysteine residues, e.g. R181C, G185C, and Y205C. To explain the loss of receptor function two mechanistic models were suggested: First, the introduction of an additional extracellular Cys residue disrupts the conserved disulfide bond connecting the first and the second extracellular loop. And second, the mutationally introduced Cys residue forms a second disulfide bond with a free Cys residue within the second exoloop. Herein, we took advantage of a new NDI-causing mutation Y205H which affects a codon frequently found to be mutated to Cys in NDI patients. In contrast to Y205C the two mechanisms described above cannot account for the loss of receptor function of Y205H. In-depth functional characterization of mutant AVPR2 showed that also for Y205C the lack of a Tyr residue at position 205 is responsible for the abolished receptor function rather than the formation of a disastrous second disulfide bond. The concerted experimental and phylogenetic analysis emphasizes that Y205 is a key residue in maintaining the structure of AVPR2 and other members of the vasopressin receptor family. © 2005 Wiley-Liss, Inc.
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=3750
Sangkuhl, K., Römpler, H., Busch, W., Karges, B., Schöneberg, T. (2005):
Nephrogenic diabetes insipidus caused by mutation of Tyr205: A key residue of V2 vasopressin receptor function
Hum. Mutat. 25 (5), 505 10.1002/humu.9337