Uncovering the biophysical mechanism of Receptor for Advanced Glycation Endproducts molecular function

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Proteins in the cell membrane play a role in integrating the cell with its surrounding environment. For example, the receptor for advanced glycation endproducts (called RAGE) has many functions including a role in immunity. An important aspect of membrane protein function is the ability to move throughout the entire cell membrane to interact with other biological components, and characterizing this movement is critical to understanding how these proteins function. This project provides missing information to advance the understanding of how other biological components affect RAGE movement in the cell membrane. The award also enables the training of graduate, undergraduate and high school students. Partners in these endeavors include two programs: one pre-college program aimed to increase the number of ethnically diverse Iowa students who pursue science degrees and the other aimed to helps Iowans understand biotechnology developments. The Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Emily A. Smith from Iowa State University to characterize the effects of chemically-defined ligand binding events, cytoplasmic interactions, and other membrane components on RAGE diffusion and clustering using fluorescence microscopy combined with live cell measurements. The primary microscopy techniques to be used include single particle tracking, fluorescence resonance energy transfer and fluorescence recovery after photobleaching. Details of the molecular mechanism of a pattern-recognition receptor including the effects of ligand affinity, valency, and chemical composition on RAGE clustering and diffusion will be elucidated for the first time. This project provides missing information to advance the understanding of an important receptor associated with innate immunity and numerous pathophysiological conditions.