Clostridium Difficile Toxin B - Structure

Structure

Toxin B (TcdB) is a cytotoxin that has a molecular weight of 270 kDa and an isoelectric point, pl, of 4.1. Toxin B has four different structural domains: catalytic, cysteine protease, translocation, and receptor binding. The N-terminal glucosyltransferase catalytic domain includes amino acid residues 1-544 while the cysteine protease domain includes residues 545-801. Additionally, the translocation region incorporates amino acid residues from 802-1664 while the receptor binding region is part of the C-terminal region and includes amino acid residues from 1665 to 2366.

The glycosylation activity of toxin B occurs in the N-terminal catalytic region (residues 1-544. This region glycosylates substrates independent of any cytotoxic activity. However, a small deletion of the receptor binding region causes attenuation of toxin B activity. The translocation region contains a hydrophobic stalk-like structure which may help residues 958-1130 in forming membrane spanning pores. The receptor binding region that includes the C-terminal repetitive region (CRR) increases the TcdB membrane interaction but does not participate in pore formation. In addition, cysteine protease and translocation regions both have complex structures which play an important functional role in translocation and receptor binding. However, deleting the translocation region of amino acids decreases the cytotoxic activity 4-fold. Both cysteine proteases and a majority of translocation regions harbor hydrophobic proteins, which show access to TcdB and other toxins crossing the cell membranes.