|
Figure 1.
Figure 1. Structural Overview of TRADD-N and the
TRADD-N/TRAF2 Complex(A) Ribbon representation of TRADD-N,
showing the two-layer arrangement of the α-β sandwich. Helices
are colored yellow (A-F), β strands blue (1–4), and loops
green. The β sheet is entirely antiparallel and slightly
twisted with a strand order of β2, β3, β1, and β4. There are
two helices each in the β1-β2 and β3-β4 cross-over
connections while the β2-β3 connection is hairpin-like. The
remaining two helices (E and F) are near the carboxyl terminus
of the domain; the loop in between (EF loop) partly covers one
end of the exposed face of the β sheet. A single hydrophobic
core is present in TRADD-N between the buried face of the β
sheet and the opposing α helices. The closed nature of this
hydrophobic core supports that this domain folds independently
of the carboxy-terminal death domain.(B and C) Ribbon
representations of the TRADD-N/TRAF2 complex, showing with the
3-fold axis vertical in (B) and into the page in (C). Three
molecules of TRADD-N are shown respectively in magenta, red, and
yellow. The protomers of the trimeric TRAF domain of TRAF2 are
shown respectively in cyan, green, and dark blue. The death
domain of TRADD (TRADD-C) is proposed to be locate above the
C-terminal helix of TRADD-N in (B).(D) A hypothetical
molecular arrangement in the signaling complex of TNFR1 and
related death receptors. The cell membrane is represented in
yellow. The trimeric TNFα, shown by ovals, mediates TNFR1
trimerization. TNFR1 is shown by straight rectangles, while FADD
and RIP are shown by bent rectangles. Death domains in TNFR1,
TRADD (labeled as TRADD-C), FADD, and RIP are shaded in gray.
TRADD-N and the TRAF domain of TRAF2 are highlighted using the
same color-coding in (B) and (C). cIAPs (oval shape) are
recruited by TRAF2 and shown to inhibit caspase activation by
this signaling complex. For clarity, only single molecules of
FADD and RIP are shown, even though they are expected to
multimerize in the signaling complex.
|
