Scc4 (CT663)

Structure and binding studies of the bi-functional Chlamydia trachomatis protein, Scc4 (CT663)

Chlamydia trachomatis infects 2.8 million people annually in the United States and can cause reproductive health complications and pneumonia in infants born to infected women. In the body, the pathogen undergoes an essential developmental process from infectious elementary bodies (EBs) that enter host cells to actively dividing, reticulate bodies (RBs). This unique cycle depends on the virulence-associated type III secretory system (T3SS), where class I T3SS dimer chaperones are required to secret virulence factors that allow C. trachomatis to infect and multiply within host cells as EBs.

Scc4 (formerly CT663) is a unique, cytosolic C. trachomatis protein that functions as both a class I T3SS chaperone and an RNA polymerase binding protein. As a chaperone, Scc4 binds Scc1 to stabilize the essential virulence factor, CopN. The long-term goal of this project is to disrupt infectious EB formation by inhibiting Scc4's activity as a chaperone and/or transcription factor. In order to identify and develop drugs to disrupt Scc4's activities, we are currently determining the high-resolution structure of Scc4 and the Scc4:Scc1 complex and characterizing the interactions of Scc4 with its ligands, Scc1 and CopN. This work is being done in collaboration with Dr. Li Shen, Associate Professor of Microbiology, Immunology and Parasitology at LSU Health Sciences Center.

Charya Wickramasinghe is the lead graduate student on this project. She mentors and trains three undergraduate researchers, Anne D'Armond, Juliette Lincoln, and Peter Howard. Each undergraduate has an independent Scc4 sub-project.

This project is supported by NIH R15 GM109413.

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