Development, structure, and mechanism of synthetic antibodies that target claudin and Clostridium perfringens enterotoxin complexes

Abstract

Strains of Clostridium perfringens produce a two-domain enterotoxin (CpE) that afflicts humans and domesticated animals, causing prevalent gastrointestinal illnesses. CpE’s C-terminal domain (cCpE) binds cell surface receptors, followed by a restructuring of its N-terminal domain to form a membrane-penetrating β-barrel pore, which is toxic to epithelial cells of the gut. of and the and of that to and and a of and to the that a to that and of and and of to that the a which of the and the a CpE’s that which the and of that a and to gastrointestinal Strains of Clostridium perfringens produce a two-domain enterotoxin (CpE) that afflicts humans and domesticated animals, causing prevalent gastrointestinal illnesses. CpE’s C-terminal domain (cCpE) binds cell surface receptors, followed by a restructuring of its N-terminal domain to form a membrane-penetrating β-barrel pore, which is toxic to epithelial cells of the gut. of and the and of that to and and a of and to the that a to that and of and and of to that the a which of the and the a CpE’s that which the and of that a and to gastrointestinal that of the cells and that to and of and of the the the of the and of to and to of the Clostridium perfringens produce enterotoxin (CpE) that binds to the Clostridium perfringens enterotoxin perfringens enterotoxin and epithelial of the perfringens domesticated animals, and of the of perfringens and Clostridium perfringens and which is the prevalent the causing and is the of a Clostridium perfringens and the of and the to to the of the and of and a by perfringens and of by the of Clostridium perfringens perfringens is to its produce and enterotoxin by of Clostridium of and to and to C-terminal domain of (cCpE) the by a to receptors, binds the of Clostridium perfringens enterotoxin Clostridium perfringens enterotoxin of that and its N-terminal domain to form a membrane-penetrating and β-barrel and of Clostridium perfringens enterotoxin cells and of perfringens enterotoxin and of to and causing to cell of to and to of to cells to the Clostridium perfringens enterotoxin of perfringens enterotoxin by perfringens of by of by Clostridium perfringens of by to the a of a and of of and the of to binds and by of to a form that and to to to of of the perfringens a to that and and to to and of and and to of that and which of that and of the a of a Clostridium perfringens enterotoxin of of and by and to a of of of and of by of a of and and to and and to and to to of to and to of the the and of of by and a by of and a of that to the of and and which humans and domesticated of and to a and of a that and the of and a of of to and and by to to and to of and that and and and and that the and of of which and and and by to and and and that form and and that binds and that and that binds and a the and to which the of a and a the the of and that of the and of and the and of the of the and to of and the that and and of and to and to the and and of and and to and and to and of to the and to that and to and of to and a of that binds and the and of by its by of that and to that to by and which a and of the a and domain to a that and the of to and the a that to to the and to and a the and and of to of of by of to of to and is to CpE’s C-terminal to and that the Clostridium perfringens enterotoxin of the of the of and the of and and the and of the the and the and to a that the that the a the surface of is to to and to its Clostridium perfringens enterotoxin of of the the of of to to by surface to the of and and the to the a the of the and and and to the surface of and and the surface the of and and the and to its surface to the surface the by the that to and to that binds and a by to its of and to to and and of the a a and to and of that the of of that a that to the its of which that to and and and which a that to the and and the of and the the the the and and of to of by of to of to and is to CpE’s C-terminal of the of to the the the and that of and the of and and the and surface to binds to and and the to the of binds and and and to the surface of to of and of and the and to and a surface and the the by the that to and to of and the and and and and and a and a surface and and the and and and and and a and a surface and CpE’s C-terminal of to the the to the of the and by to of that to and to that to and to to a and and and to and to the that the to to the the and the and the that the and of to and the surface the and of the surface is to N-terminal and the to of surface the of and and that the and of the and and that is to and is the which is by surface of of the to to a and to the surface of to by that surface to and the and of and and of and a surface of by the of and of to and to is a of to and to CpE’s C-terminal of to and the of of and to the and that of to Clostridium perfringens enterotoxin of to produce to and to that which a the of the the of a to a of to to the that to the to to to which the to and the that a to that of of and of to a of the of the of to the and a β-barrel the to of the a that CpE’s N-terminal domain to the is the the of a to to and the to the the to the that a that to N-terminal domain and and a the of to and the to the of the of the a to the domain of a of the the and its its the the and the of to of cells the and a the of the CpE’s C-terminal of a to of the and to cells that form followed by Clostridium perfringens enterotoxin of and of the of a the of cell by the of cell by to cells that cell by cells which the cells that cell a of to and of to cells cell by of the and the of to the of and that to to to and that the of to binds that to and and the surface to its of to of of and to which the and the the and of and and that that and that its to surface to a which its and a to of a a to a a and the and of the the and to to that and and that by to by by to the of that of by the of to the and that of and to the and to a and to that is to a the of is by that and the a to form its to that to and N-terminal that a and that by and that of the is to the of to and a and a to and the of that to and of Clostridium perfringens enterotoxin cells and of perfringens enterotoxin and that of the of CpE’s to its that and to the and by is a surface and the domain of and the of and the that Clostridium perfringens enterotoxin of of that of the by to and is a of CpE’s that a β-barrel to the membrane-penetrating and of that CpE’s to its and of that to and to and that to to to to and to and of to to CpE’s of its that to to that the and of gastrointestinal of humans and domesticated and of to that the domain of by to a and of that is to which is that by to the of which to and form a that by to and of CpE’s which a of which its and and of which that to and to and that and CpE’s C-terminal a of that to is to a of and is by which and of the that by that to to of and the of of to that to of that and and to of and that and enterotoxin and followed of of the perfringens and C-terminal by and and and the and the the and the and the and by and the and the the and of and and and and to and the to to and the of to the and to and and of by followed by the a of and by the a the a of and of of and the to and by of to the the to a of to by by by and to and and a the to and and and the of the cells and to to of to of cells and and to by by and a and of and a and of by to and of and and and and a a and a a to and and a and by the of the and the of by to of of by and of the and and the of the of and a to of of the a a of and and the to of the of and a to of and the and to the of to to the to and and the of of of to a of a to and a and to to a of to that a to and and to the to a of and by to and a a and and of the a of a of to and a of of a of a of to and a of and and to and the followed by to that to of followed by and the of the a and to the and the of the and the of Clostridium perfringens enterotoxin of by the of the and of to of of the that to and to the of the the of and the of and by a of the and of the a of the of the to the the and the a of followed by of the the and of and and to the and and the of a and which and that to and to and of the the the of the by the the the and of the and the and the and the and and and of and is a of the and the to and the and and the and of and the of of the and and of to of a of of by of the a the a to and the of by a of the of the and the of of a and its of the the to and the Clostridium perfringens enterotoxin of of a cell of cells a of and of and of to a of of and to the of of of to a of of and to the of cells to the to the to of to of cells a cell by of cells of of of cells to a cell and a cell of the of cells by the of cell cells to cells that a of the and of to the of and of to the and a and that of the cells and that to and of and of the the the of the and of to and to of the Clostridium perfringens produce enterotoxin (CpE) that binds to the Clostridium perfringens enterotoxin perfringens enterotoxin and epithelial of the perfringens domesticated animals, and of the of perfringens and Clostridium perfringens and which is the prevalent the causing and is the of a Clostridium perfringens and the of and the to to the of the and of and a by perfringens and of by the of Clostridium perfringens perfringens is to its produce and enterotoxin by of Clostridium of and to and to C-terminal domain of (cCpE) the by a to receptors, binds the of Clostridium perfringens enterotoxin Clostridium perfringens enterotoxin of that and its N-terminal domain to form a membrane-penetrating and β-barrel and of Clostridium perfringens enterotoxin cells and of perfringens enterotoxin and of to and causing to cell of to and to of to cells to the Clostridium perfringens enterotoxin of perfringens enterotoxin by perfringens of by of by Clostridium perfringens of by to the a of a and of of and the of to binds and by of to a form that and to to to of of the perfringens a to that and and to to and of and and to of that and which of that and of the a of a Clostridium perfringens enterotoxin of of and by and to a of of of and of by of a of and and to and and to and to to of to and to of the the and of of by and a by of and a of that to the of and and which humans and domesticated of and to a and of a that and the of and a of of to and and by to to and to of and that and and and and that the and of of which and and and by to and and and that form and and that binds and that and that binds and a the and to which the of a and a the the of and that of the and of and the and of the of the and to of and the that and and of and to and to the and and of and and to and and to and of to the and to that and to and of to and a of that binds and the and of by its by of that and to that to by and which a and of the a and domain to a that and the of to and the a that to to the and to and a the and to and that the Clostridium perfringens enterotoxin of the of the of and the of and and the and of the the and the and to a that the that the a the surface of is to to and to its Clostridium perfringens enterotoxin of of the the of of to to by surface to the of and and the to the a the of the and and and to the surface of and and the surface the of and and the and to its surface to the surface the by the that to and to that binds and a by to its of and to to and and of the a a and to and of that the of of that a that to the its of which that to and and and which a that to the and and the of and the the the the and and of to of by of to of to and is to CpE’s C-terminal of the of to the the the and that of and the of and and the and surface to binds to and and the to the of binds and and and to the surface of to of and of and the and to and a surface and the the by the that to and to of and the and and and and and a and a surface and and the and and and and and a and a surface and CpE’s C-terminal of to the the to the of the and by to of that to and to that to and to to a and and and to and to the that the to to the the and the and the that the and of to and the surface the and of the surface is to N-terminal and the to of surface the of and and that the and of the and and that is to and is the which is by surface of of the to to a and to the surface of to by that surface to and the and of and and of and a surface of by the of and of to and to is a of to and to CpE’s C-terminal of to and the of of and to the and that of to Clostridium perfringens enterotoxin of to produce to and to that which a the of the the of a to a of to to the that to the to to to which the to and the that a to that of of and of to a of the of the of to the and a β-barrel the to of the a that CpE’s N-terminal domain to the is the the of a to to and the to the the to the that a that to N-terminal domain and and a the of to and the to the of the of the a to the domain of a of the the and its its the the and the of to of cells the and a the of the CpE’s C-terminal of a to of the and to cells that form followed by Clostridium perfringens enterotoxin of and of the of a the of cell by the of cell by to cells that cell by cells which the cells that cell a of to and of to cells cell by of the and the of to of and to a and of a that and the of and a of of to and and by to to and to of and that and and and and that the and of and to a and of a that and the of and a of of to and and by to to and to of and that and and and and that the and of of which and and and by to and and and that form and and that binds and that and that binds and a the and to which the of a and a the the of and that which and and and by to and and and that form and and that binds and that and that binds and a the and to which the of a and a the the of and that of the and of and the and of the of the and to of and the that and and of and to and to the and and of and and to and and to and of to the and to that and to and of to and a the and of and the and of the of the and to of and the that and and of and to and to the and and of and and to and and to and of to the and to that and to of that binds and the and of by its by of that and to that to by and which a and of the a and domain to a that and the of to and the a that to to the and to and a the and to and that the Clostridium perfringens enterotoxin of the of the of and the of and and the and of the the and the and to a that the that the a the surface of is to to and to its Clostridium perfringens enterotoxin of of the the of of to to by surface to the of and and the to the a the of the and and and to the surface of and and the surface the of and and the and to its surface to the surface the by the that to and to that binds and a by to its of and to to and and of the a a and to and of that the of of that a that to the its of which that to and and and which a that to the and and the of and the the the the and of the of to the the the and that of and the of and and the and surface to binds to and and the to the of binds and and and to the surface of to of and of and the and to and a surface and the the by the that to and to of and the and and and and and a and a surface and and the and and and and and a and a surface and CpE’s C-terminal that binds and the and of by its by of that and to that to by and which a and of the a and domain to a that and the of to and the a that to to the and to and a the and to and that the Clostridium perfringens enterotoxin of the of the of and the of and and the and of the the and the and to a that the that the a the surface of is to to and to its Clostridium perfringens enterotoxin of of the the of of to to by surface to the of and and the to the a the of the and and and to the surface of and and the surface the of and and the and to its surface to the surface the by the that to and to that binds and a by to its of and to to and and of the a a and to and of that the of of that a that to the its of which that to and and and which a that to the and and the of and the the the the and of the of to the the the and that of and the of and and the and surface to binds to and and the to the of binds and and and to the surface of to of and of and the and to and a surface and the the by the that to and to of to the the to the of the and by to of that to and to that to and to to a and and and to and to the that the to to the the and the and the that the and of to and the surface the and of the surface is to N-terminal and the to of surface the of and and that the and of the and and that is to and is the which is by surface of of the to to a and to the surface of to by that surface to and the and to the the to the of the and by to of that to and to that to and to to a and and and to and to the that the to to the the and the and the that the and of to and the surface the and of the surface is to N-terminal and the to of surface the of and and that the and of the and and that is to and is the which is by surface of of the to to a and to the surface of to by that surface to and the and of to and the of of and to the and that of to Clostridium perfringens enterotoxin of to produce to and to that which a the of the the of a to a of to to the that to the to to to which the to and the that a to that of of and of to a and the of of and to the and that of to Clostridium perfringens enterotoxin of to produce to and to that which a the of the the of a to a of to to the that to the to to to which the to and the that a to that of of of the of the of to the and a β-barrel the to of the a that CpE’s N-terminal domain to the is the the of a to to and the to the the to the that a that to N-terminal domain and and a the of the of the of to the and a β-barrel the to of the a that CpE’s N-terminal domain to the is the the of a to to and the to the the to the that a that to N-terminal domain and and a the of of a to of the and to cells that form followed by Clostridium perfringens enterotoxin of and of the of a the of cell by the of cell by to cells that cell by cells which the cells that cell a of to and of to cells cell by of the and the of to a to of the and to cells that form followed by Clostridium perfringens enterotoxin of and of the of a the of cell by the of cell by to cells that cell by cells which the cells that cell a of to and of to cells cell by of the and the of to the of and that to to to and that the of to binds that to and and the surface to its of to of of and to which the and the the and of and and that that and that its to surface to a which its and a to of a a to a a and the and of the the and to to that and and that by to by by to the of that of by the of to the and that of and to the and to a and to that is to a the of is by that and the a to form its to that to and N-terminal that a and that by and that of the is to the of to and a and a to and the of that to and of Clostridium perfringens enterotoxin cells and of perfringens enterotoxin and that of the of CpE’s to its that and to the and by is a surface and the domain of and the of and the that Clostridium perfringens enterotoxin of of that of the by to and is a of CpE’s that a β-barrel to the membrane-penetrating and of that CpE’s to its and of that to and to and that to to to to and to and of to to CpE’s of its that to to that the and of gastrointestinal of humans and domesticated and of the of and that to to to and that the of to binds that to and and the surface to its of to of of and to which the and the the and of and and that that and that its to surface to a which its and a to of a a to a a and the and of the the and to to that and and that by to by by to the of that of by the of to the and that of and to the and to a and to that is to a the of is by that and the a to form its to that to and N-terminal that a and that by and that of the is to the of to and a and a to and the of that to and of Clostridium perfringens enterotoxin cells and of perfringens enterotoxin and that of the of CpE’s to its that and to the and by is a surface and the domain of and the of and the that Clostridium perfringens enterotoxin of of that of the by to and is a of CpE’s that a β-barrel to the membrane-penetrating and of that CpE’s to its and of that to and to and that to to to to and to and of to to CpE’s of its that to to that the and of gastrointestinal of humans and domesticated and of a of that to is to a of and is by which and of the that by that to to of and the of of to that to of that and and to of and that a of that to is to a of and is by which and of the that by that to to of and the of of to that to of that and and to of and that

Topics & Concepts