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Nephrogenic diabetes insipidus caused by mutation of Tyr205: a key residue of V2 vasopressin receptor function.
Hum Mutat. 2005 May; 25(5):505.HM

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.

Authors+Show Affiliations

Institute of Biochemistry, Dept. of Molecular Biochemistry, Medical Faculty, University of Leipzig, Leipzig, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15841479

Citation

Sangkuhl, Katrin, et al. "Nephrogenic Diabetes Insipidus Caused By Mutation of Tyr205: a Key Residue of V2 Vasopressin Receptor Function." Human Mutation, vol. 25, no. 5, 2005, p. 505.
Sangkuhl K, Römpler H, Busch W, et al. Nephrogenic diabetes insipidus caused by mutation of Tyr205: a key residue of V2 vasopressin receptor function. Hum Mutat. 2005;25(5):505.
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. Human Mutation, 25(5), 505.
Sangkuhl K, et al. Nephrogenic Diabetes Insipidus Caused By Mutation of Tyr205: a Key Residue of V2 Vasopressin Receptor Function. Hum Mutat. 2005;25(5):505. PubMed PMID: 15841479.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nephrogenic diabetes insipidus caused by mutation of Tyr205: a key residue of V2 vasopressin receptor function. AU - Sangkuhl,Katrin, AU - Römpler,Holger, AU - Busch,Wibke, AU - Karges,Beate, AU - Schöneberg,Torsten, PY - 2005/4/21/pubmed PY - 2006/6/6/medline PY - 2005/4/21/entrez SP - 505 EP - 505 JF - Human mutation JO - Hum Mutat VL - 25 IS - 5 N2 - 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. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/15841479/Nephrogenic_diabetes_insipidus_caused_by_mutation_of_Tyr205:_a_key_residue_of_V2_vasopressin_receptor_function_ L2 - https://doi.org/10.1002/humu.9337 DB - PRIME DP - Unbound Medicine ER -