Reengineering anthrax toxin protective antigen for improved receptor-specific protein delivery.

ABSTRACT:

Background

To increase the size of the druggable proteome, it would be highly desirable to devise efficient methods to translocate designed binding proteins to the cytosol, as they could specifically target flat and hydrophobic protein-protein interfaces. If this could be done in a manner dependent on a cell surface receptor, two layers of specificity would be obtained: one for the cell type and the other for the cytosolic target. Bacterial protein toxins have naturally evolved such systems. Anthrax toxin consists of a pore-forming translocation unit (protective antigen (PA)) and a separate protein payload. When engineering PA to ablate binding to its own receptor and instead binding to a receptor of choice, by fusing a designed ankyrin repeat protein (DARPin), uptake in new cell t

SUBMITTER: Becker L 

PROVIDER: S-EPMC7427085 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature