Intracellular disassembly and activity of pertussis toxin require interaction with ATP. 2016

Roger D Plaut, and Karen M Scanlon, and Michael Taylor, and Ken Teter, and Nicholas H Carbonetti
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

The active subunit (S1) of pertussis toxin (PT), a major virulence factor of Bordetella pertussis, ADP-ribosylates Gi proteins in the mammalian cell cytosol to inhibit GPCR signaling. The intracellular pathway of PT includes endocytosis and retrograde transport to the trans-Golgi network (TGN) and endoplasmic reticulum (ER). Subsequent translocation of S1 to the cytosol is presumably preceded by dissociation from the holotoxin. In vitro, such dissociation is stimulated by interaction of PT with ATP. To investigate the role of this interaction in cellular events, we engineered a form of PT (PTDM) with changes to two amino acids involved in the interaction with ATP. PTDM was reduced in (1) binding to ATP, (2) dissociability by interaction with ATP, (3) in vitro enzymatic activity and (4) cellular ADP-ribosylation activity. In cells treated with PTDM carrying target sequences for organelle-specific modifications, normal transport to the TGN and ER occurred, but N-glycosylation patterns of the S1 and S4 subunits were consistent with an inability of PTDM to dissociate in the ER. These results indicate a requirement for interaction with ATP for PT dissociation in the ER and cellular activity. They also indicate that the retrograde transport route is the cellular intoxication pathway for PT.

UI MeSH Term Description Entries
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D042541 Intracellular Space The area within CELLS. Subcellular Space,Intracellular Spaces,Space, Intracellular,Space, Subcellular,Spaces, Intracellular,Spaces, Subcellular,Subcellular Spaces
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D021122 Protein Subunits Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly. Protomers,Protein Subunit,Protomer,Subunit, Protein,Subunits, Protein
D021381 Protein Transport The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport. Cellular Protein Targeting,Gated Protein Transport,Protein Targeting, Cellular,Protein Translocation,Transmembrane Protein Transport,Vesicular Protein Transport,Protein Localization Processes, Cellular,Protein Sorting,Protein Trafficking,Protein Transport, Gated,Protein Transport, Transmembrane,Protein Transport, Vesicular,Traffickings, Protein
D037342 Pertussis Toxin One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity. IAP Pertussis Toxin,Islet-Activating Protein,Pertussigen,Histamine-Sensitizing Factor,Islets-Activating Protein,Lymphocytosis-Promoting Factor,Histamine Sensitizing Factor,Islet Activating Protein,Islets Activating Protein,Lymphocytosis Promoting Factor,Pertussis Toxin, IAP,Toxin, IAP Pertussis,Toxin, Pertussis

Related Publications

Roger D Plaut, and Karen M Scanlon, and Michael Taylor, and Ken Teter, and Nicholas H Carbonetti
July 1990, Biochemistry,
Roger D Plaut, and Karen M Scanlon, and Michael Taylor, and Ken Teter, and Nicholas H Carbonetti
July 2019, Toxins,
Roger D Plaut, and Karen M Scanlon, and Michael Taylor, and Ken Teter, and Nicholas H Carbonetti
July 1992, The Journal of biological chemistry,
Roger D Plaut, and Karen M Scanlon, and Michael Taylor, and Ken Teter, and Nicholas H Carbonetti
December 1992, Infection and immunity,
Roger D Plaut, and Karen M Scanlon, and Michael Taylor, and Ken Teter, and Nicholas H Carbonetti
January 1993, The Journal of biological chemistry,
Roger D Plaut, and Karen M Scanlon, and Michael Taylor, and Ken Teter, and Nicholas H Carbonetti
October 1984, Infection and immunity,
Roger D Plaut, and Karen M Scanlon, and Michael Taylor, and Ken Teter, and Nicholas H Carbonetti
November 1984, Infection and immunity,
Roger D Plaut, and Karen M Scanlon, and Michael Taylor, and Ken Teter, and Nicholas H Carbonetti
March 2001, Cellular microbiology,
Roger D Plaut, and Karen M Scanlon, and Michael Taylor, and Ken Teter, and Nicholas H Carbonetti
September 1987, Journal of general microbiology,
Roger D Plaut, and Karen M Scanlon, and Michael Taylor, and Ken Teter, and Nicholas H Carbonetti
September 1989, The Biochemical journal,
Copied contents to your clipboard!