ABSTRACT

I. INTRODUCTION 95 II. A BRIEF DESCRIPTION OF DIPHTHERIA TOXIN 96

III. DIFFERENCES IN THE SENSITIVITY OF CELLS TO DIPHTHERIA TOXIN 97

IV. BIOCHEMICAL STUDIES OF THE DIPHTHERIA TOXIN RECEPTOR 98 A. Binding of Diphtheria Toxin to Intact Cells 98 B. Identification and Purification of the Diphtheria Toxin Receptor 99

v. GENETIC APPROACHES TO THE DIPHTHERIA TOXIN RECEPTOR 101 VI. RECEPTOR STRUCTURE AND REQUIREMENTS FOR DIPHTHERIA

TOXIN BINDING 102 VII. MOLECULES ASSOCIATED WITH THE DIPHTHERIA TOXIN

RECEPTOR 103 VIII. THE RECEPTOR AND THE DIPHTHERIA TOXIN ENTRY PROCESS 104

IX. THE DIPHTHERIA TOXIN RECEPTOR AS A GROWTH FACTOR 105

X. CONCLUSION 105

REFERENCES 106

Since the discovery by Roux of its role in the disease caused by Corynebacterium diphtheriae, diphtheria toxin (DT) has been studied first for the prevention of disease and later to understand the pathogenic mechanism at the molecular level. A number of important

discoveries in the field of bacterial pathogenesis and bacterial protein toxins have resulted from these studies; for example, ( 1) antibodies directed against the toxin can protect against the disease, (2) diphtheria toxin acts within cells by inactivating a target protein by ADP-ribosylation, and (3) the toxin consists of two segments with distinct functions. Because of extensive studies over a long period, diphtheria toxin is one of the best known of the bacterial protein toxins, and discoveries such as those enumerated above have frequently led to increased understanding of the biology of other bacterial toxins.