Gram-positive secretion chaperone-client interactions

Our research program focuses on post-translocation secretion chaperones in Gram-positive bacteria, so as to better understand the processes underlying protein secretion, activity, and regulation following membrane translocation. Currently, little is known about post-translocation protein folding in Gram-positive bacteria which presents a barrier to understanding the core biology of these organisms and how they interact with their environment. We hypothesize that Gram-positive secretion chaperones regulate proper folding, stabilization, and activity of secreted proteins that contribute to bacterial physiology. We use two model organisms, Listeria monocytogenes and Streptococcus pneumoniae as tools to determine secretion chaperone activities and mechanisms that are both broadly conserved and species-specific. Gram-positive bacteria encode secretion chaperones that belong to two distinct peptidyl-prolyl isomerases (PPIases) families which include PrsA homologs from the parvulin PPIases and SlrA homologs from the cyclophilin PPIases. Over the next 5 years, we will identify and characterize these secretion chaperone-client repertoires, identify chaperone domains critical for client interactions, and elucidate molecular mechanisms of chaperone-client interactions and regulation. We anticipate that the goals proposed in this grant will have broad relevance to several Gram- positive post-translocation secretion mechanisms. Therefore, by defining paradigms of Gram-positive secretion chaperone-client activation and regulation, we will provide novel insight into the molecular mechanisms governing the core biology of these fascinating organisms. Project Number: 1R35GM159731-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Laty Cahoon | Institution: UNIVERSITY OF PITTSBURGH AT PITTSBURGH, PITTSBURGH, PA | Award Amount: $401,939 | Activity Code: R35 | Study Section: Maximizing Investigators' Research Award B Study Section[MRAB] View on NIH RePORTER: https://reporter.nih.gov/project-details/11199395