UbcM2 has a severely limited capacity to synthesize
polyUb chains
on AO7T with wt Ub. (A) Fully recombinant in vitro ubiquitylation assays containing recombinant E1, H6T-UbcM2,
wt Ub, energy, and [35S]AO7T (produced in a bacterial TNT
expression system) were incubated at 37 °C for the indicated
times. Reaction mixtures were solubilized and processed for SDS–PAGE
and fluorography. (B) Same as panel A except testing H6T-UbcH5b. For panels A and B, [35S]AO7T input was loaded
to the left of lane 1 and the migration of molecular weight markers
is denoted on the left. Unmodified [35S]AO7T is marked
on the right of each fluorograph with a hashmark and Ub-modified [35S]AO7T [[35S]AO7T-(Ub)n] with a vertical line. (C) Assay similar to that in panel A except
wt Ub has been replaced with lysine-less Ub (UbK0). Distinct
bands representing the attachment of one, two, three, or four monoUbK0 molecules to AO7T are denoted with asterisks between lanes
2 and 3 and lanes 3 and 4. (D) Assay similar to that in panel C except
that HA-AO7T is not radiolabeled with [35S]Met/Cys but
rather reaction products are visualized by either anti-Ub (top) or
anti-HA Western blotting (bottom). The number of UbK0 molecules
conjugated to HA-AO7T is indicated to the right of each blot. The
sensitivity of the anti-Ub antibody is such that only HA-AO7T modified
with either three or four UbK0 molecules is detected. All
experiments were repeated at least three independent times.