Role of low complexity sequences in promoting
the release of a
fragment from the proteasome. (A) A protein targeted to the proteasome
from the C-terminus will have the C-terminal portion of the protein
degraded (green domain), but the presence of a low complexity region
and an additional tightly folded domain (blue domain) leads to the
release of a fragment consisting of the domain and a tail composed
of part or all of the low complexity region. Only the endpoint of
degradation is shown. (B) With a normal, high complexity sequence
adjacent to the blue domain, a degradation intermediate will form
composed of the blue domain bound to the proteasome. This intermediate
will then partition between release and degradation, with degradation
typically being faster (thicker arrow) leading to overall degradation
of the fragment. (C) With a low complexity sequence adjacent to the
blue domain, unfolding and degradation is slowed with little or no
effect on release, leading to an overall reduction in degradation
and accumulation of stable fragment, the same endpoint as shown in
plot (A).