DeNiro, Adara; Cao, Erhu; Wang, Qinzhe; Wang, Jinliang (University of Utah)
Faculty Advisor: Cao, Erhu (University of Utah, School of Medicine)
The kidneys are responsible for several essential bodily functions critical to our survival. These include filtering blood and excreting metabolic waste into urine. Two proteins, polycystin-1 and polycystin-2, interact in renal tubules and promote the normal development and function of the kidneys. However, the proteins' actions are not well understood. Polycystin-1 and Polycystin-2 are encoded by the PKD1 gene and the PKD2 gene respectively. A mutation in either of these genes can lead to Autosomal Dominant Polycystic Kidney Disease (ADPKD), a common inherited disease leading to progressive renal failure. Several extrarenal manifestations occur as a result of ADPKD including hepatic cysts and intracranial aneurysms. Ultimately, ADPKD often leads to end-stage renal disease that requires dialysis or transplantation. Currently, there is no cure for ADPKD due to setbacks regarding structural determination of the Polycystic Kidney Disease Proteins. Some setbacks are the inability to view the regulatory cytosolic domains of the PKD1/PKD2 channel in atomic detail and understand the function(s) of the polycystic kidney disease proteins. My project examines the ability of Fabs and nanobodies to bind to the PKD2 channel and the PKD1/2 complex as this potentially facilitates structural determination. This is done by stabilizing cytosolic domains and/or promoting a more uniform orientation distribution of these proteins essential for imaging by cryo-electron microscopy.