Diphtheria Toxin - Structure

Structure

Diphtheria toxin is a single polypeptide chain of 535 amino acids consisting of two subunits linked by disulfide bridges, known as an A-B toxin. Binding to the cell surface of the B subunit (the less stable of the two subunits) allows the A subunit (the more stable part of the protein) to penetrate the host cell.

The crystal structure of the diphtheria toxin homodimer has been determined to 2.5A resolution. The structure reveals a Y-shaped molecule consisting of 3 domains. Fragment A contains the catalytic C domain, and fragment B consists of the T and R domains

  • The N-terminal catalytic domain, known as the C domain, has an unusual beta+alpha fold. The C domain blocks protein synthesis by transfer of ADP-ribose from NAD to a diphthamide residue of EF-2.
  • A central translocation domain, known as the T domain or TM domain. The T domain has a multi-helical globin-like fold with two additional helices at N-termini, but which has no counterpart to the first globin helix. This domain is thought to unfold in the membrane. pH-induced conformational change in the T domain triggers insertion into the endosomal membrane and facilitates the transfer of the C domain into the cytoplasm.
  • A C-terminal receptor-binding domain, known as the R domain. This domain has a beta-sandwich fold consisting of nine strands in two sheets with greek-key topology; it is a subclass of immunoglobin-like fold. The R domain binds to cell surface receptor, permitting the toxin to enter the cell by receptor mediated endocytosis.

Read more about this topic:  Diphtheria Toxin

Famous quotes containing the word structure:

    “I really do inhabit a system in which words are capable of shaking the entire structure of government, where words can prove mightier than ten military divisions.”
    —Václav Havel (b. 1936)

    “A committee is organic rather than mechanical in its nature: it is not a structure but a plant. It takes root and grows, it flowers, wilts, and dies, scattering the seed from which other committees will bloom in their turn.”
    —C. Northcote Parkinson (1909–1993)

    “Each structure and institution here was so primitive that you could at once refer it to its source; but our buildings commonly suggest neither their origin nor their purpose.”
    —Henry David Thoreau (1817–1862)