TRAF2, TRAF3, and TRAF5 bind to the
carboxyl-terminal conserved domain, but TRAF6 binds to the N-terminal
domain in CD40cyt. (A) Alignment of human and mouse CD40cyt.
The carboxyl-terminal part of CD40cyt is identical between hCD40 and
mCD40, but the N-terminal part is poorly conserved. Conserved residues
substituted in mutagenesis described in the text are indicated by
boxes, and the resulting aas by the mutagenesis are shown above these
boxes. GST-tagged hCD40cyt constructs (cyt, cyt-N and cyt-C) are shown
below the sequences. (B) In vivo association
of TRAFs with GST-hCD40 in 293T cells. Cell extracts from 293T cells
cotransfected with expression plasmids for Flag-tagged TRAFs and
GST-tagged hCD40cyt or its deletion mutants were prepared. The GST
pulldown assays were performed and TRAF proteins bound to beads were
then analyzed by Western blotting by using anti-Flag antibody M2
(Top). One-tenth of GST fusion proteins attached to
beads was separated on 12.5% polyacrylamide/SDS gel and visualized
by Coomassie brilliant blue R-250 staining
(Bottom). A portion of the lysate used for the GST
pulldown assay was separated on 8.5% polyacrylamide/SDS gel and
expression level of Flag-tagged TRAFs was analyzed by Western blotting
by using anti-Flag antibody M2 (Middle).