Assignment 2

     Vasopressin is a small peptide hormone that is 9 amino acids long. It is encoded for by a gene that is on the 20th chromosome and is at the AAA64291 locust. The precursor protein is 164 amino acids long. Vasopressin itself starts at the 20th amino acid and ends at the 28th amino acid and has the sequence cyfqncprg.

Figure 1: Amino acid sequence of Vasopressin and Oxytosin

Some of the domains that have been identified on the human version of the vasopressin precursor are a signaling peptide (aa 1-19), neurophysin (aa 32-122), a neurohypophysial hormone region (aa 39-166) and a glycopeptide (aa 124-164). The signal domain is not a typical promoter that is found regulating other genes. It is thought that this is an atypical promoter to promote cell specific expression of the protein. The role of the neurophysin is not thought to be biologicaly active, but instead is thought to help in the protection of vasopressin from enzymatic cleavage. The tyrosine residue of vasopressin is essential for association with neurophysin and transport within the cell. The glycopeptide is used to help vasopressin fold when there is low amounts of glycopeptides in the cell. Once vasopressin has been folded properly it can be secreted.

The receptor for vasopressin has been determined to be the vasopressin V2 receptor. It is 164 amino acids long spans the membrane several times. The gene encoding for this receptor is located on the gene region Xq28. It consists of three exons and two introns. An extra cellular component of the receptor binds with vasopressin that leads to a cascade the results in the cAMP being formed and eventually having more aquaporins inserted in to the membrane of the collecting ducts. The V2 receptor is a G protein. The 8th residue of vasopressin interacts with the first extracellular loop to initiate the cascade that eventually results in aquaporins being added to the collection tubule.

The disulfinde bond that gives vasopressin a ring can be seen in Figure 1. Also seen in figure 1 is oxytosin. It can be noted how similar they are in sequence only varying at the 8th residue. There is evidently not a lot of variation that exist in these molecules and have them still have the same structure. This becomes even more evident when the protein sequence for vasopressin of multiple animals are lined up. The protein itself is highly conserved especially throughout the four mamals.

Figure 2: Multiple alingment of prepropeptide of Vasopressin.
vasopressin is highlted in yellow

The neurophysin domain that come after the vasopressin domain is also well conserved between species. It is probably due to the fact that neurophysin is necessairy for proper folding of vasopressin. The rest of the domains are not well conserved between all of the species. This is not surprising as the organisms selected are very evolutionary divers. A closer look however will indicate the mammals share a large amount of sequence similarity in the glycopeptide sequence. There is a lot more to be learned about the structure of vasopressin and its receptor.