MOLECULAR DETERMINANTS OF ANTHRAX TOXIN TRANSLOCATION

Harvard Medical School, Boston MA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): How proteins, which are composed of both hydrophobic and hydrophilic amino acid residues, are translocated across hydrophobic lipid bilayers has been the subject of intense scrutiny. In the case of anthrax toxin, Bacillus anthracis secretes a translocase component called protective antigen (PA) that creates a conduit through which the separately secreted toxic enzymatic moieties termed lethal and edema factors (LF and EF respectively) are transported. Far from a passive channel, the PA pore plays an active role in translocation by binding the N-terminus of EF/LF and catalyzing the subsequent translocation by interacting with residues in EF/LF as they traverse the pore. In this application, the sequence- and structure-specific means by which the enzymatic moieties are recognized and transported through the narrow tunnel created by the PA pore will be investigated using synthetic peptide techniques together with planar lipid bilayer electrophysiology methods. Addressing these research questions will provide an understanding of the principles that govern translocation through the anthrax toxin pore, and further will aid in the design of inhibitors that block the pathogenesis of anthrax. [unreadable] [unreadable] [unreadable]