Triggers and switches in a self-assembling pore-forming protein.

Protein engineering is being used to produce a collection of pore-forming proteins with applications in biotechnology. Knowledge provided by investigations of the mechanism of self-assembly of staphylococcal alpha-hemolysin has allowed the design of genetically and chemically modified variants of the protein with pore-forming activities that can be triggered or switched on-and-off by chemical, biochemical and physical inputs. Examples include alpha-hemolysins that are activated by specific proteases and alpha a-hemolysins whose activity is controlled by divalent metal ions. These proteins have potential value in drug delivery as components of immunotoxins that can be activated at the surfaces of target cells. Further applications are likely in improved encapsulation techniques for drugs, enzymes and cells.