Researcher Liang Feng, Associate Professor of Molecular and Cellular Physiology at Stanford University, and Research Fellow Xue Guo received a grant award in 2020 to continue their work on the Molecular Mechanism of Cystinosis. The objectives of this study are to understand several key aspects of how membrane proteins that have important implications in cystinosis work at the molecular level.
Membrane proteins are dynamic and often undergo significant conformational transitions to carry out their functions. Alteration in conformational equilibrium or transition is among the fundamental mechanisms underlying dysfunction of membrane proteins caused by disease-related mutations. Membrane proteins play key roles in maintaining lysosomal homeostasis and have important implications in cystinosis. To understand the molecular basis underlying conformational transitions of membrane proteins, we used spectroscopic studies to characterize their conformational equilibrium in a well-defined system. In these studies, the proteins were labeled with probes, and our results suggested transitions between different conformations. These studies set the stage to probe how disease-causing mutations affect dynamic properties of membrane proteins and will help provide insights into the cause and potential therapy for cystinosis.