2000 Global Researcher Conference Proceeding
March 10 - 12, 2000
|Conference:||2000 Global Researcher Conference|
|Title:||Functional rescue of three vasopressin V2 receptor mutants causing nephrogenic diabetes insipidus by a second site suppressor mutation|
|Authors:||Schulein, Ralf; Zuhlke, Kerstin; Rosenthal, Walter|
|Institutions:||Forschungsinstitut fur Molekulare Pharmakologie (FMP), Forschungsinstitut fur Molekulare Pharmakologie, Charite - Universitatsmedizin Berlin|
The vasopressin-2 receptor (V2R) is a protein made up of a specific sequence of amino acids configured in a specific shape. Amino acids that combine to form a protein undergo a slight chemical change and are called residues. Rosenthal, et al., examined three mutant V2Rs, all of which had a cysteine residue (C) where there should have been another type of residue. In each case, the C was assumed to alter the shape of the V2R by impairing the formation of the normal disulfide bond that occurs in normal V2Rs. This structural alteration affected the function of the three mutant V2Rs in different ways. In two of the mutants, it prevents the V2Rs from forming a bond with the antidiuretic hormone, arginine vasopressin (AVP). The other mutant was unable to travel to the cell membrane where it must be if it is to bind with AVP.
The researchers introduced a second mutation into each of these mutants, an additional A taking the place of the normally occurring C residue at position 195 of the amino acid sequence of the V2R. This manipulation allowed each of the mutants now to function normally. The researchers suggest the functional rescue occurs because the mutation-causing additional C in each of the three original mutants each form a second disulfide bond with the C at position 195 which was eliminated by the second mutation.