EXROP Projects: Tom A. Rapoport

Tom A. Rapoport
Summer Lab Size: 20
Local Summer Program: Harvard EXROP Summer Experience
Program Dates: June 8-August 15, 2015 (Dates for 2016 should be similar)

Structural Studies of Protein Translocation in Bacterial Pathogenecity

Despite the wide variety of antibiotics available today, bacterial infections remain the most common diseases in humans. Pathogenic gram-positive and mycobacteria are the main species contributing to the most prevalent bacterial infections. Both types of organisms export virulence factors via an accessory protein translocation system. In Streptococcus bacteria, the accessory secretion system exports only one protein, an adhesion protein that allows the bacterium to attach to the host cell. This project aims to investigate the mechanism of accessory protein translocation. The adhesion protein is glycosylated in the cytosol before export from the cell, the glycosylated form is then recognized by three different targeting proteins, and finally the protein is exported by a dedicated ATPase through a membrane channel. The project for the EXROP student will involve structural studies of the targeting proteins. The student will make mutations in the proteins, crystallize mutants, and perform functional studies. The goal is a better understanding of the role of the targeting factors in accessory protein secretion.

Mechanistic Studies of Accessory Protein Translocation

Despite the wide variety of antibiotics available today, bacterial infections remain the most common diseases in humans. Pathogenic gram-positive and mycobacteria are the main species contributing to the most prevalent bacterial infections. Both types of organisms export virulence factors via an accessory protein translocation system. In Streptococcus bacteria, the accessory secretion system exports only one protein, an adhesion protein that allows the bacterium to attach to the host cell. This project aims to investigate the mechanism of accessory protein translocation. The adhesion protein is glycosylated in the cytosol before export from the cell, the glycosylated form is then recognized by three different targeting proteins, and finally the protein is exported by a dedicated ATPase through a membrane channel. The project for the EXROP student will involve structural studies on the targeting proteins. The student will make mutations in the proteins, crystallize mutants, and perform functional studies. The goal is a better understanding of the role of the targeting factors in accessory protein secretion.

Scientist Profile

Investigator
Harvard Medical School
Cell Biology, Structural Biology