Transport of diphtheria toxin A fragment across the plasma membrane.
The 60,000-dalton diphtheria toxin molecule is synthesized and released from the bacteria as a single polypeptide chain which may be subdivided into three functional regions of approximately equal length. There is an enzymically active 21,150-dalton A fragment extending from the N-terminal glycine residue to the first of the two disulfide bridges. This hydrophilic, negatively charged polypeptide must cross the plasma membrane of the target cell and reach the cytoplasm in order to inactivate EF-2 by ADP-ribosylation and thereby block protein synthesis. There is a C-terminal postiviely charged polypeptide sequence of 10,000--20,000 daltons which interacts with specific receptors present on the membranes of sensitive cells and which includes the second cystine disulfide. Between these two hydrophilic regions there is an hydrophobic zone which, when "unmasked," is capable of binding about 44 molecules of the nonionic detergent Triton X-100 and readily becomes inserted into membrane vesicles. It is suggested that the entry process involves an initial reversible interaction with membrane receptors, followed by an irreversible process in which the C-terminal region is released by a proteolytic cleavage, thus permitting the hydrophobic portion of the molecule to enter the lipid bilayer and form a channel through which the A fragment is drawn in an extended form to reach the cytoplasm.
D000818:Animals; D001665:Binding Sites; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D004167:Diphtheria Toxin / Q000378:metabolism*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism
D002352:Carrier Proteins; D004167:Diphtheria Toxin; D010446:Peptide Fragments