 |
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
DOI no:
|
J Biol Chem
275:31171-31177
(2000)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Crystal structure of TRAIL-DR5 complex identifies a critical role of the unique frame insertion in conferring recognition specificity.
|
|
S.S.Cha,
B.J.Sung,
Y.A.Kim,
Y.L.Song,
H.J.Kim,
S.Kim,
M.S.Lee,
B.H.Oh.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
TRAIL is a cytokine that induces apoptosis in a wide variety of tumor cells but
rarely in normal cells. It contains an extraordinarily elongated loop because of
an unique insertion of 12-16 amino acids compared with the other members of
tumor necrosis factor family. Biological implication of the frame insertion has
not been clarified. We have determined the crystal structure of TRAIL in a
complex with the extracellular domain of death receptor DR5 at 2.2 A resolution.
The structure reveals extensive contacts between the elongated loop and DR5 in
an interaction mode that would not be allowed without the frame insertion. These
interactions are missing in the structures of the complex determined by others
recently. This observation, along with structure-inspired deletion analysis,
identifies the critical role of the frame insertion as a molecular strategy
conferring specificity upon the recognition of cognate receptors. The structure
also suggests that a built-in flexibility of the tumor necrosis factor receptor
family members is likely to play a general and important role in the binding and
recognition of tumor necrosis factor family members.
|
|
|
|
|
|
| |
Selected figure(s)
|
|
|
|
| |
|
|
|
|
|
|
Figure 3.
Fig. 3. Superposition of the ligand-receptor complexes
and that of sDR5 molecules. A, the TRAIL-sDR5 and TNF   sTNFR55
complexes are superposed using only the structurally conserved C
 atoms on
the -sheets of
the ligand molecules. C atoms are
shown with the omission of TNF . sDR5 and
sTNFR55 are shown in green and violet, respectively. TRAIL is in
light green. B, the six sDR5 molecules with the ordered B2
modules in three TRAIL-sDR5 complex structures are superposed,
showing the variation in the relative position of the B2 module
in CDR2.
|
|
Figure 4.
Fig. 4. The central contact region. A, surface
representation of TRAIL-sDR5 exhibiting crevices at the binding
interface that accommodate the penetration of the AA" loop.
Positive, neutral, and negative electrostatic potentials are
colored blue, white, and red, respectively. The molecular
surfaces are drawn without residues 130-135, which is shown in
sticks. Dots indicate a putative course of the disordered region
starting from Leu-136 on the AA" loop. B, a simulated annealing
2F[o] F[c] omit
map contoured at 1  . At a
refinement stage with an R value of 25%, the structure was
disturbed at 1000 K with the omission of residues 130-135 of the
AA" loop and the residues within 3.5 Å from the segment,
and then the map was calculated with the same omission. C, the
interactions mediated by residues 131-135 of TRAIL. The
intramolecular interaction of Arg-130 is not shown. The N1
module, CRD1, and CRD2 in sDR5 are represented by pink, yellow,
and reddish brown, respectively. Residues 130-135 in TRAIL are
in cyan. Oxygen and nitrogen atoms are in red and blue,
respectively. White dotted lines indicate hydrogen bonds.
|
|
|
|
|
|
| |
The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2000,
275,
31171-31177)
copyright 2000.
|
|
| |
Figures were
selected
by an automated process.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
Literature references that cite this PDB file's
key reference
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
M.Tarrus,
A.M.van der Sloot,
K.Temming,
M.Lacombe,
F.Opdam,
W.J.Quax,
G.Molema,
K.Poelstra,
and
R.J.Kok
(2008).
RGD-avidin-biotin pretargeting to alpha(v)beta (3) integrin enhances the proapoptotic activity of TNFalpha related apoptosis inducing ligand (TRAIL).
|
| |
Apoptosis, 13,
225-235.
|
|
|
|
|
|
|
T.A.Wassenaar,
W.J.Quax,
and
A.E.Mark
(2008).
The conformation of the extracellular binding domain of Death Receptor 5 in the presence and absence of the activating ligand TRAIL: a molecular dynamics study.
|
| |
Proteins, 70,
333-343.
|
|
|
|
|
|
|
F.K.Chan
(2007).
Three is better than one: pre-ligand receptor assembly in the regulation of TNF receptor signaling.
|
| |
Cytokine, 37,
101-107.
|
|
|
|
|
|
|
A.M.van der Sloot,
V.Tur,
E.Szegezdi,
M.M.Mullally,
R.H.Cool,
A.Samali,
L.Serrano,
and
W.J.Quax
(2006).
Designed tumor necrosis factor-related apoptosis-inducing ligand variants initiating apoptosis exclusively via the DR5 receptor.
|
| |
Proc Natl Acad Sci U S A, 103,
8634-8639.
|
|
|
|
|
|
|
L.Clancy,
K.Mruk,
K.Archer,
M.Woelfel,
J.Mongkolsapaya,
G.Screaton,
M.J.Lenardo,
and
F.K.Chan
(2005).
Preligand assembly domain-mediated ligand-independent association between TRAIL receptor 4 (TR4) and TR2 regulates TRAIL-induced apoptosis.
|
| |
Proc Natl Acad Sci U S A, 102,
18099-18104.
|
|
|
|
|
|
|
S.Bouralexis,
D.M.Findlay,
and
A.Evdokiou
(2005).
Death to the bad guys: targeting cancer via Apo2L/TRAIL.
|
| |
Apoptosis, 10,
35-51.
|
|
|
|
|
|
|
S.W.Fesik
(2005).
Promoting apoptosis as a strategy for cancer drug discovery.
|
| |
Nat Rev Cancer, 5,
876-885.
|
|
|
|
|
|
|
T.Mori,
A.Oguro,
T.Ohtsu,
and
Y.Nakamura
(2004).
RNA aptamers selected against the receptor activator of NF-kappaB acquire general affinity to proteins of the tumor necrosis factor receptor family.
|
| |
Nucleic Acids Res, 32,
6120-6128.
|
|
|
|
|
|
|
D.A.Oren,
Y.Li,
Y.Volovik,
T.S.Morris,
C.Dharia,
K.Das,
O.Galperina,
R.Gentz,
and
E.Arnold
(2002).
Structural basis of BLyS receptor recognition.
|
| |
Nat Struct Biol, 9,
288-292.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
G.H.Nam,
and
K.Y.Choi
(2002).
Association of human tumor necrosis factor-related apoptosis inducing ligand with membrane upon acidification.
|
| |
Eur J Biochem, 269,
5280-5287.
|
|
|
|
|
|
|
J.Lam,
C.A.Nelson,
F.P.Ross,
S.L.Teitelbaum,
and
D.H.Fremont
(2001).
Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity.
|
| |
J Clin Invest, 108,
971-979.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
R.L.Rich,
and
D.G.Myszka
(2001).
Survey of the year 2000 commercial optical biosensor literature.
|
| |
J Mol Recognit, 14,
273-294.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
|
90 a.a.
110 a.a.
152 a.a.
_ZN
