Sandbox Reserved 1237: Difference between revisions

Verotoxin-1 exists as hetero-hexamer (~74300 Da), made up of an A and B subunit. The A-subunit, a monomer, is ~32000 Da, while each of the five chains of the B-subunit pentamer is ~8000-8500 Da. Thus, the protein stoichiometry is A5B. The A By itself, the B subunit has cyclic C5 symmetry. It is the A subunit that causes disease via catalytically inactivating 60S ribosomal subunit by cleaving into subunits A1 and A2 via furin, A1 being the catalytic unit and A2 being the unit binding A1 to the β pentamer. The role of the B subunit is to bind to receptors on target cells, most notably globotriaosylceramide (Gb3) in humans. There are three Gb3 binding sites within the B subunit, sites 1 and 2 having a higher affinity than site 3. Thus, the A subunit is the disease-causing subunit. The A1 subunit contains ten alpha-helices and thirteen beta-strands while the A2 subunit contain two alpha-helices and two beta-strands. The A2 subunit is also entirely hydrophilic while the A1 subunit has regions of hydrophobicity, likely due to its function as a catalytic inhibitor of the 60S subunit. The B subunit is largely hydrophilic with one region of hydrophobicity, which are alpha-to-beta transitions on the outer side of the pentamer. [1][2]