A Role for K268 in V2R Folding
| Title: | A Role for K268 in V2R Folding |
|---|---|
| Authors: | Le Gouill, Christian; Darden, Thomas; Madziva, Michael T.; Birnbaumer, Mariel |
| Publisher: | FEBS Letters |
| Date Published: | September 12, 2005 |
| Reference Number: | 695 |
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
The vasopressin 2 receptor protein (V2R) plays an essential role in the kidney’s ability to reabsorb water and hence concentrate urine. V2R is synthesized in the cell interior and must travel to the cell membrane to perform its function, which is to bind with the hormone, arginine vasopressin (AVP). The binding of AVP and V2R initiates a chemical sequence that allows the principal cells of the kidney collecting duct to absorb water.
Scientists have constructed a model of the shape of the V2R based on inference and experimentation. It is thought to be a chain of 271 amino acid residues, part of which is inside the cell membrane (which forms the perimeter of the cell), part of it is inside the cell, and part is outside the cell. The part inside the membrane is called the transmembrane domain (TM, and there are seven of them, TM 1 – TM 7). The parts inside the cell are called the intracellular loops (iloop); there are four of them (iloop 1 – iloop 4). There are four extracellular loops (eloop 1 – eloop 4). The amino acids that comprise V2R are in a specific order. For example, K268 denotes that a lysine amino acid (K) is the 268th amino acid in the chain of 271 amino acids in the V2R.
The placement of the amino acids is important because the way they interact within the protein helps fold the V2R into its proper shape. Some amino acids carry a positive charge, others don’t. Some appear vital for proper V2R function, others not as vital. Mutations in the V2R can result in NDI so researchers try to get an ever more accurate picture of the V2R’s exact shape and orientation in the cell.
Le Gouill, et al., performed an extensive series of experiments on the V2R by changing amino acids of the V2R. The researchers then tested the modified V2R to see how well it was expressed (i.e., how many numbers of them were synthesized) and how well they bound with AVP and initiated the sequence that led to urine concentration.
They concluded that K268 (i.e., a lysine amino acid that is the 268th amino acid in the V2R) is essential for the V2R to fold into its proper configuration and therefore, this positively charged amino acid is essential for V2R expression. Further, K268 probably assures the proper activation of the G proteins, a necessary step for the urine concentration process to occur. The research team’s efforts suggest that K268 is located at the boundary of the 3i loop and TM 6. Their data suggests that the two stems of the 3i loop, that is of TM 5 and 6, are close together. These findings refine the V2R model and provide a clearer understanding of the V2R structure.