The three-dimensional structure of "escherichia coli" heat-labile enterotoxin in relation to its function

Heat labile enterotoxin (LT) from Escherichia coli is a major virulence factor of enterotoxigenic E. coli strains (ETEC), which cause a generally mild diarrhea in human beings and domestic animals. It is one of the major causes of traveller's diarrhea and as such usually harmless. In small children in third world countries, however, it can lead to dehydration and death. Through the high incidence of the disease this occasional effect still causes larges numbers of victims. Heat labile enterotoxin has a very high similarity, both in sequence and activity, to cholera toxin (CT), the major virulence factor of the cholera-causing bacteria Vibrio cholerae O1. This thesis describes the crystallographic three dimensional structure determination of heat labile enterotoxin, followed by a detailed analysis of the structure itself, a comparison to exotoxin A and verotoxin, and a number of structure-based functional studies on the binding of the membrane receptor and the relative flexibility of the subunits. Zie: Summary.