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:

    Agnosticism is a perfectly respectable and tenable philosophical position; it is not dogmatic and makes no pronouncements about the ultimate truths of the universe. It remains open to evidence and persuasion; lacking faith, it nevertheless does not deride faith. Atheism, on the other hand, is as unyielding and dogmatic about religious belief as true believers are about heathens. It tries to use reason to demolish a structure that is not built upon reason.
    Sydney J. Harris (1917–1986)

    Science is intimately integrated with the whole social structure and cultural tradition. They mutually support one other—only in certain types of society can science flourish, and conversely without a continuous and healthy development and application of science such a society cannot function properly.
    Talcott Parsons (1902–1979)

    The question is still asked of women: “How do you propose to answer the need for child care?” That is an obvious attempt to structure conflict in the old terms. The questions are rather: “If we as a human community want children, how does the total society propose to provide for them?”
    Jean Baker Miller (20th century)