2004 Global Researcher Conference Proceeding
April 09 - 11, 2004
|Conference:||2004 Global Researcher Conference|
|Title:||Structural evolution of the V2 vasopressin receptor in mammals|
|Authors:||Rompler, Holger; Busch, Wibke; Pitra, Christian; Schoneberg, Torsten; Schulz, Angela|
|Institutions:||University of Leipzig, Institute for Zoo and Wildlife Research|
The vasopressin/V2-vasopressin receptor (V2-R) system plays an important role in maintaining the water balance and electrolyte homeostasis in humans and other vertebrates. This hormone/receptor system is already present in bone fishes reflecting its evolutionary success. Within this period of 450 million years the vasopressin/V2-R system was involved in adaptation to a great variety of habitats with different accessibility to water (e.g., desert, salt water, fresh water).
Here, we set out to analyze whether different environmental conditions are reflected in the structural and functional properties of the V2-R. Thus, V2-R orthologs were cloned from mammalian species existing in extreme habitats. The sequence information of more than three dozens cloned orthologs of the V2-R enabled us to identify motifs and residues that are important for maintaining the receptor function. In mammalian V2-R evolution about 66% residues (between the first intracellular loop and the NPXXY-motif in TM7) were absolutely conserved between marsupials and humans and 43% between fish (zebrafish, fugu) and mammals. Interestingly, there are marked differences in the loop length of mammalian orthologs. For example, the third intracellular loop of the V2-R from marsupials is 11 amino acids shorter as compared with rodent and primate orthologs. However, the loop length has no significant influence on V2-R function. Further, we studied the genomic organization of the exon/intron structure of the V2-R gene. Interestingly, the overall genomic organization is conserved between species but e.g. the second intron varies in sequence and length.
Here we demonstrate, that mining evolution as an additional source can provide structural information which may guide the generation of a V2-R model and may help to interpret new mutations found in NDI patients.
The vasopressin-2 receptor (V2R) and its ancestor the vasotocin receptor has been around for approximately 450 million years. It is found in many different species with widely different degrees of accessibility to water. The V2R, like all proteins, is made up of a specific sequence of amino acid residues that form a specific shape. Because of the involvement of this receptor in the water-electrolyte balance, Schulz, et al., investigated whether different environmental conditions influenced different structural and functional properties in the V2Rs of mammals and fish that lived in different environments.
The researchers found that in mammals about 66% of the amino acid residues were the same. About 43% of the residues were the same when comparing fish and mammals. The V2R has several loops in it, and there are differences in loop length among different mammalian species, indicating, the loop length has no significant influence on V2R function.