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PDBsum entry 1ngr
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* Residue conservation analysis
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DOI no:
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Embo J
16:4999-5005
(1997)
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PubMed id:
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NMR structure of the death domain of the p75 neurotrophin receptor.
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E.Liepinsh,
L.L.Ilag,
G.Otting,
C.F.Ibáñez.
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ABSTRACT
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The intracellular domain of the p75 neurotrophin receptor (p75ICD) lacks
catalytic activity but contains a motif similar to death domains found in the
cytoplasmic regions of members of the tumor necrosis factor receptor family and
their downstream targets. Although some aspects of the signaling pathways
downstream of p75 have been elucidated recently, mechanisms of receptor
activation and proximal signaling events are unknown. Here we report the nuclear
magnetic resonance (NMR) structure of the 145 residue long p75ICD. The death
domain of p75ICD consists of two perpendicular sets of three helices packed into
a globular structure. The polypeptide segment connecting the transmembrane and
death domains as well as the serine/threonine-rich C-terminal end are highly
flexible in p75ICD. Unlike the death domains involved in signaling by the TNF
receptor and Fas, p75ICD does not self-associate in solution. A surface area
devoid of charged residues in the p75ICD death domain may indicate a potential
site of interaction with downstream targets.
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Selected figure(s)
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Figure 1.
Figure 1 Transverse relaxation time T[2] of the amide protons
versus the amino acid sequence of p75ICD.
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Figure 5.
Figure 5 Mapping of the amino acid sequence of TRADD onto the
death domain of p75. The death domain of p75 is drawn as a
ribbon highlighting the C^  positions
of those residues which are positively (blue) or negatively
(red) charged in TRADD. Loop regions in p75ICD corresponding to
sites in TRADD where mutations to alanine suppressed the
self-association of the TRADD death domain (Park and Baichwal,
1996) are shown in magenta (see also Figure 3).
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
Embo J
(1997,
16,
4999-5005)
copyright 1997.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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H.H.Park
(2011).
Structural analyses of death domains and their interactions.
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Apoptosis,
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Q.B.Zhang,
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(2011).
Establishment of a novel human esophageal squamous cell carcinoma cell line (ESC-410) and its partial biological characterization.
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Dis Esophagus,
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Oncogene,
29,
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K.G.Bath,
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Dev Neurobiol,
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K.K.Teng,
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Physiol Rev,
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Activation of the p75 neurotrophin receptor through conformational rearrangement of disulphide-linked receptor dimers.
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Neuron,
62,
72-83.
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Self-renewal and chemotherapy resistance of p75NTR positive cells in esophageal squamous cell carcinomas.
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BMC Cancer,
9,
9.
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C.K.Underwood,
and
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The p75 neurotrophin receptor.
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Int J Biochem Cell Biol,
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The p75 receptor is associated with inflammatory thermal hypersensitivity.
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J Neurosci Res,
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C.Stevens,
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A germ line mutation in the death domain of DAPK-1 inactivates ERK-induced apoptosis.
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J Biol Chem,
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H.H.Park,
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The death domain superfamily in intracellular signaling of apoptosis and inflammation.
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Annu Rev Immunol,
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L.He,
Y.Chen,
L.Hong,
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(2007).
p75 neurotrophin receptor suppresses the proliferation of human gastric cancer cells.
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Neoplasia,
9,
471-478.
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P.C.Sabeti,
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R.Gaudet,
S.F.Schaffner,
E.S.Lander,
K.A.Frazer,
D.G.Ballinger,
D.R.Cox,
D.A.Hinds,
L.L.Stuve,
R.A.Gibbs,
J.W.Belmont,
A.Boudreau,
P.Hardenbol,
S.M.Leal,
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D.A.Wheeler,
T.D.Willis,
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H.Yang,
C.Zeng,
Y.Gao,
H.Hu,
W.Hu,
C.Li,
W.Lin,
S.Liu,
H.Pan,
X.Tang,
J.Wang,
W.Wang,
J.Yu,
B.Zhang,
Q.Zhang,
H.Zhao,
H.Zhao,
J.Zhou,
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B.Blumenstiel,
A.Camargo,
M.Defelice,
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J.Moore,
H.Nguyen,
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M.Parkin,
J.Roy,
E.Stahl,
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L.Ziaugra,
D.Altshuler,
Y.Shen,
Z.Yao,
W.Huang,
X.Chu,
Y.He,
L.Jin,
Y.Liu,
Y.Shen,
W.Sun,
H.Wang,
Y.Wang,
Y.Wang,
X.Xiong,
L.Xu,
M.M.Waye,
S.K.Tsui,
H.Xue,
J.T.Wong,
L.M.Galver,
J.B.Fan,
K.Gunderson,
S.S.Murray,
A.R.Oliphant,
M.S.Chee,
A.Montpetit,
F.Chagnon,
V.Ferretti,
M.Leboeuf,
J.F.Olivier,
M.S.Phillips,
S.Roumy,
C.Sallée,
A.Verner,
T.J.Hudson,
P.Y.Kwok,
D.Cai,
D.C.Koboldt,
R.D.Miller,
and
L.Pawlikowska
(2007).
Genome-wide detection and characterization of positive selection in human populations.
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Nature,
449,
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T.Ozben
(2007).
Oxidative stress and apoptosis: impact on cancer therapy.
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J Pharm Sci,
96,
2181-2196.
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E.J.Coulson
(2006).
Does the p75 neurotrophin receptor mediate Abeta-induced toxicity in Alzheimer's disease?
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J Neurochem,
98,
654-660.
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J.M.Fletcher,
and
R.A.Hughes
(2006).
Novel monocyclic and bicyclic loop mimetics of brain-derived neurotrophic factor.
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J Pept Sci,
12,
515-524.
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J.Tan,
and
R.K.Shepherd
(2006).
Aminoglycoside-induced degeneration of adult spiral ganglion neurons involves differential modulation of tyrosine kinase B and p75 neurotrophin receptor signaling.
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Am J Pathol,
169,
528-543.
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L.F.Reichardt
(2006).
Neurotrophin-regulated signalling pathways.
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Philos Trans R Soc Lond B Biol Sci,
361,
1545-1564.
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M.Vilar,
M.Murillo-Carretero,
H.Mira,
K.Magnusson,
V.Besset,
and
C.F.Ibáñez
(2006).
Bex1, a novel interactor of the p75 neurotrophin receptor, links neurotrophin signaling to the cell cycle.
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EMBO J,
25,
1219-1230.
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N.Handa,
M.Kukimoto-Niino,
R.Akasaka,
K.Murayama,
T.Terada,
M.Inoue,
T.Yabuki,
M.Aoki,
E.Seki,
T.Matsuda,
E.Nunokawa,
A.Tanaka,
Y.Hayashizaki,
T.Kigawa,
M.Shirouzu,
and
S.Yokoyama
(2006).
Structure of the UNC5H2 death domain.
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Acta Crystallogr D Biol Crystallogr,
62,
1502-1509.
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PDB code:
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C.Sandu,
E.Gavathiotis,
T.Huang,
I.Wegorzewska,
and
M.H.Werner
(2005).
A mechanism for death receptor discrimination by death adaptors.
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J Biol Chem,
280,
31974-31980.
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J.P.Aurikko,
B.T.Ruotolo,
J.G.Grossmann,
M.C.Moncrieffe,
E.Stephens,
V.M.Leppänen,
C.V.Robinson,
M.Saarma,
R.A.Bradshaw,
and
T.L.Blundell
(2005).
Characterization of symmetric complexes of nerve growth factor and the ectodomain of the pan-neurotrophin receptor, p75NTR.
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J Biol Chem,
280,
33453-33460.
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T.Yamashita,
M.Fujitani,
K.Hata,
F.Mimura,
and
S.Yamagishi
(2005).
Diverse functions of the p75 neurotrophin receptor.
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Anat Sci Int,
80,
37-41.
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A.Blöchl,
L.Blumenstein,
and
M.R.Ahmadian
(2004).
Inactivation and activation of Ras by the neurotrophin receptor p75.
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Eur J Neurosci,
20,
2321-2335.
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J.M.Hill,
G.Morisawa,
T.Kim,
T.Huang,
Y.Wei,
Y.Wei,
and
M.H.Werner
(2004).
Identification of an expanded binding surface on the FADD death domain responsible for interaction with CD95/Fas.
|
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J Biol Chem,
279,
1474-1481.
|
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E.Tsukamoto,
Y.Hashimoto,
K.Kanekura,
T.Niikura,
S.Aiso,
and
I.Nishimoto
(2003).
Characterization of the toxic mechanism triggered by Alzheimer's amyloid-beta peptides via p75 neurotrophin receptor in neuronal hybrid cells.
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J Neurosci Res,
73,
627-636.
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S.Rabizadeh,
and
D.E.Bredesen
(2003).
Ten years on: mediation of cell death by the common neurotrophin receptor p75(NTR).
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Cytokine Growth Factor Rev,
14,
225-239.
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C.M.Troy,
J.E.Friedman,
and
W.J.Friedman
(2002).
Mechanisms of p75-mediated death of hippocampal neurons. Role of caspases.
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J Biol Chem,
277,
34295-34302.
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G.Perini,
V.Della-Bianca,
V.Politi,
G.Della Valle,
I.Dal-Pra,
F.Rossi,
and
U.Armato
(2002).
Role of p75 neurotrophin receptor in the neurotoxicity by beta-amyloid peptides and synergistic effect of inflammatory cytokines.
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J Exp Med,
195,
907-918.
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J.Mukai,
S.Shoji,
M.T.Kimura,
S.Okubo,
H.Sano,
P.Suvanto,
Y.Li,
S.Irie,
and
T.A.Sato
(2002).
Structure-function analysis of NADE: identification of regions that mediate nerve growth factor-induced apoptosis.
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J Biol Chem,
277,
13973-13982.
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M.L.Medina,
B.S.Chapman,
J.P.Bolender,
and
L.A.Plesniak
(2002).
Transient vesicle leakage initiated by a synthetic apoptotic peptide derived from the death domain of neurotrophin receptor, p75NTR.
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J Pept Res,
59,
149-158.
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M.Tcherpakov,
F.C.Bronfman,
S.G.Conticello,
A.Vaskovsky,
Z.Levy,
M.Niinobe,
K.Yoshikawa,
E.Arenas,
and
M.Fainzilber
(2002).
The p75 neurotrophin receptor interacts with multiple MAGE proteins.
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J Biol Chem,
277,
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J Neurosci Res,
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C.Tornatore,
and
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TrkA induces differentiation but not apoptosis in C6-2B glioma cells.
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J Neurosci Res,
64,
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C.H.Weber,
and
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The death domain superfamily: a tale of two interfaces?
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Trends Biochem Sci,
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Annu Rev Neurosci,
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Curr Opin Neurobiol,
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G.De Wilde,
J.Murray-Rust,
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N.Q.McDonald,
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A.Wollmer,
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(2001).
Structure-activity relationship of the p55 TNF receptor death domain and its lymphoproliferation mutants.
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Eur J Biochem,
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M.V.Sofroniew,
C.L.Howe,
and
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Annu Rev Neurosci,
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Protein Sci,
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A.H.Salehi,
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(2000).
NRAGE, a novel MAGE protein, interacts with the p75 neurotrophin receptor and facilitates nerve growth factor-dependent apoptosis.
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Neuron,
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Curr Opin Neurobiol,
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ICEBERG: a novel inhibitor of interleukin-1beta generation.
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Cell,
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PDB code:
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J.C.Reed
(2000).
Mechanisms of apoptosis.
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Am J Pathol,
157,
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J.J.Gentry,
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(2000).
Nerve growth factor activation of nuclear factor kappaB through its p75 receptor is an anti-apoptotic signal in RN22 schwannoma cells.
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J Biol Chem,
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J.J.Wang,
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J Neurosci Res,
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D.Schmidt,
and
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(2000).
NGF ligand alters NGF signaling via p75(NTR) and trkA.
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J Neurosci Res,
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P.S.Sastry,
and
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(2000).
Apoptosis and the nervous system.
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J Neurochem,
74,
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R.T.Dobrowsky,
and
B.D.Carter
(2000).
p75 neurotrophin receptor signaling: mechanisms for neurotrophic modulation of cell stress?
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J Neurosci Res,
61,
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S.W.Fesik
(2000).
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Cell,
103,
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S.Wang,
P.Bray,
T.McCaffrey,
K.March,
B.L.Hempstead,
and
R.Kraemer
(2000).
p75(NTR) mediates neurotrophin-induced apoptosis of vascular smooth muscle cells.
|
| |
Am J Pathol,
157,
1247-1258.
|
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T.Raveh,
H.Berissi,
M.Eisenstein,
T.Spivak,
and
A.Kimchi
(2000).
A functional genetic screen identifies regions at the C-terminal tail and death-domain of death-associated protein kinase that are critical for its proapoptotic activity.
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| |
Proc Natl Acad Sci U S A,
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A.Chittka,
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(1999).
Identification of a zinc finger protein whose subcellular distribution is regulated by serum and nerve growth factor.
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Proc Natl Acad Sci U S A,
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A.V.Kovalenko,
and
M.P.Boldin
(1999).
Tumor necrosis factor receptor and Fas signaling mechanisms.
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E.Casademunt,
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G.Dechant,
and
Y.A.Barde
(1999).
The zinc finger protein NRIF interacts with the neurotrophin receptor p75(NTR) and participates in programmed cell death.
|
| |
EMBO J,
18,
6050-6061.
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p75 neurotrophin receptor-mediated neuronal death is promoted by Bcl-2 and prevented by Bcl-xL.
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J Biol Chem,
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Signaling of neuronal cell death by the p75NTR neurotrophin receptor.
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Mol Neurobiol,
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The solution structure of FADD death domain. Structural basis of death domain interactions of Fas and FADD.
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J Biol Chem,
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PDB code:
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G.Khursigara,
J.R.Orlinick,
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Association of the p75 neurotrophin receptor with TRAF6.
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Three-dimensional structure of a complex between the death domains of Pelle and Tube.
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Cell,
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545-555.
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PDB code:
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T.Yamashita,
K.L.Tucker,
and
Y.A.Barde
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Neurotrophin binding to the p75 receptor modulates Rho activity and axonal outgrowth.
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Neuron,
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Low-affinity nerve-growth factor receptor (P75NTR) can serve as a receptor for rabies virus.
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Solution structure of the RAIDD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment.
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PDB code:
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W.M.ElShamy,
L.K.Fridvall,
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Growth arrest failure, G1 restriction point override, and S phase death of sensory precursor cells in the absence of neurotrophin-3.
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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.
|
|
Links
