Periplasmic Chaperone Network Organization and Mechanism

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This discovery project investigates the maturation processes of beneficial microorganisms found in humans. These microbes have sugar- and fat-filled membrane surfaces that encapsulate their cells. Proteins are embedded within the sugar/fat mixture, and their proper incorporation is essential for the integrity and functions of these surfaces. This project addresses how these three types of molecules come together. A series of systematic investigations will be conducted to determine the molecular structures of helper proteins that play key roles in the assembly process. A second part of the project will use pictures of living cells to discover the surface distribution of these helper proteins throughout the cell. Are these helper proteins clumping all together in a cell? Or are they sprinkled evenly throughout? In addition, the PI will broaden the participation in science through research opportunities for graduate and undergraduate students, by nurturing a more inclusive climate in graduate and undergraduate STEM education, and by teaching using evidence-based best practices. The goals of this project are to investigate the periplasmic chaperone network organization and mechanism. This will be achieved using two general approaches. The first is to determine the solution structures of two of the soluble chaperone proteins in complex with an unfolded outer membrane protein. This will be accomplished by integrating information from orthogonal, biophysical methods and computational modeling. The outcome from this effort will be novel structures that provide key information on how these chaperones ensure efficient outer membrane protein biogenesis by maintaining unfolded membrane proteins in solution. The second fundamental effort addressed in this project is to examine the periplasmic distribution of a key chaperone in living cells using imaging techniques. The main question in this latter effort is to evaluate whether or not soluble chaperones are well mixed in this unique cellular compartment that lacks any external energy source. Together the outcomes will provide a fundamental understanding of membrane protein biogenesis in bacteria. This information can be used to infer mechanistic insights into homologous system in mitochondria of eukaryotes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.