2020 USRA - Structural NMR studies of human Aquaporin 2

Job Information

Structural NMR studies of human Aquaporin 2

Proposed start date:  May 4, 2020

Job Description

Student will be responsible for NMR data collection and processing, data analysis. 
Preferred qualification: understanding of principles of protein structure, analytical skills, some programming experience, common sense


Vladimir Ladizhansky, Professor
Department of Physics

Brief Outline of Proposed Research Project

Water reabsorption in kidneys is an important physiological process mediated by several forms of human aquaporins (hAQPs), homotetrameric helical membrane proteins serving as selective water channels. The major players in water reabsorption in kidneys are hAQP1 and hAQP2. HAQP2 plays critical role in concentrating urine; regulation of its activity occurs by translocating the protein from intracellular vesicles to the apical plasma membrane.  Misregulation of hAQP2 trafficking results in a severe polyuric condition known as nephrogenic diabetes insipidus (NDI). There are more than 50 known mutations of hAQP2 responsible for NDI.  We are interested to identify conformational changes in hAQP2 that result from mutations, and to determine how they interfere with hAQP2 trafficking. We propose to use solid-state Nuclear Magnetic Resonance spectroscopy (SSNMR) to characterize these changes. The main goal of this project is to determine SSNMR chemical shifts (frequencies) of individual atoms of hAQP2. The chemical shifts will be used to analyse the conformational state of the wild type (unmutated) hAQP2; they will serve as structural reporters that would allow to track conformational changes caused by mutations.