(A) Gel-filtration analysis of purified Strep-tagged
unphosphorylated STAT1 (uSTAT1) and phosphorylated-Tyr701-STAT1 (pSTAT1),
importin α5 (Impα5) and varying molar mixtures of pSTAT1 and
Impα5. Free pSTAT1 elutes at 9.7 ml (presumably in a dimer-tetramer
equilibrium) and free uSTAT1 at 11 ml (presumably as a dimer); the
pSTAT1:importin α5 complexes formed at different molar ratios of
pSTAT1 and Impα5 elute at identical elution volumes of 10.5 ml. Free
Impα5, and excess Impα5 not bound in the pSTAT1:importin
α5 complex elutes at 13.5 ml. (B) The indicated elution
fractions obtained from the gel-filtration analyses of pSTAT1:importin
α5 complexes shown in (A) were analyzed by Western Blot
with anti-Strep antibody after 10% SDS-PAGE. (C)
Sedimentation velocity analyses of uSTAT1, pSTAT1, importin α5, and
complexes thereof. Graphical representation of molecular species detected by
genetic algorithm–Monte Carlo analysis with molecular weights (M.W.)
and frictional ratio in pseudo-3D plots. Left panel, Impα5, uSTAT1,
and pSTAT1 were analyzed separately. Note an additional high molecular
weight peak for pSTAT1 consistent with tetramerization (asterisk). Right
panel, Impα:pSTAT1 was mixed and gel-filtrated. The peak fraction
containing Impα:pSTAT1 complex was used in the ultracentrifugation
experiment. Two molecular species with molecular weights of ~180 kDa
and ~245 kDa were present. The latter was assigned to represent
pSTAT1:importin α5 complex, whereas the former represents free
pSTAT1 dimers. Asterisk, co-sedimenting salt in the reference cell.