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PDBsum entry 4pp8
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Immune system
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PDB id
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4pp8
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Contents |
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125 a.a.
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146 a.a.
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150 a.a.
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References listed in PDB file
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Key reference
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Title
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Crystal structures of rae-1beta and its complex with the activating immunoreceptor nkg2d.
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Authors
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P.Li,
G.Mcdermott,
R.K.Strong.
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Ref.
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Immunity, 2002,
16,
77-86.
[DOI no: ]
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PubMed id
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Abstract
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Induced by retinoic acid and implicated in playing a role in development, rodent
RAE-1 proteins are ligands for the activating immunoreceptor NKG2D, widely
expressed on natural killer cells, T cells, and macrophages. RAE-1 proteins
(alpha, beta, gamma, and delta) are distant major histocompatibility complex
(MHC) class I homologs, comprising isolated alpha1alpha2 platform domains. The
crystal structure of RAE-1beta was distorted from other MHC homologs and
displayed noncanonical disulfide bonds. The loss of any remnant of a peptide
binding groove was facilitated by the close approach of the groove-defining
helices through a hydrophobic, leucine-rich interface. The RAE-1beta-murine
NKG2D complex structure resembled the human NKG2D-MICA receptor-ligand complex
and further demonstrated the promiscuity of the NKG2D ligand binding site.
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Figure 3.
Figure 3. Structures of Murine NKD NK Cell Receptor-Ligand
ComplexesRibbon representations (top) and GRASP (Nicholls et
al., 1991) molecular surfaces (bottom) are shown for the
structures of (A) the muNKG2D–RAE-1β, (B) huNKG2D–MICA, and
(C) Ly49A-H-2D^d complexes. Ribbons of the ligands are colored
by domain: α1, yellow; α2, red; α3 (when present), green; and
β[2]-m (when present), cyan; ribbons of the receptors are
colored by chain: blue or purple. Molecular surfaces of the
platform domains are oriented such that the view is looking down
onto the NKG2D binding surface of RAE-1 and MICA. In (A), the
molecular surface of muNKG2D was included in an orientation
looking down onto the RAE-1 binding surface, as if the receptor
had been peeled away from the complex. Molecular surfaces are
colored by electrostatic potential, with positively charged
areas in blue and negatively charged areas in red. In (C), the
bound peptide in H-2D^d is shown in ball-and-stick
representation.
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Figure 4.
Figure 4. Interactions of RAE-1β-muNKG2D Complexes in the
CrystalTwo views of the reciprocal, crystallographic interaction
between muNKG2D homodimers are shown, a view perpendicular to a
hypothetical cell-cell interface (top) and a view down onto the
complexes (bottom). Molecules are shown as ribbon
representations colored by domain (muNKG2D-A, blue; muNKG2D-B,
purple; RAE-1β α1, yellow; and RAE-1β α2, orange). The
approximate position of the crystallographic 6[1] screw axis is
indicated, as are hypothetical cell surfaces and the paths of
membrane anchor elements (black arrows). The position of Asn179
is indicated in red on the ribbons and by red arrows.
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The above figures are
reprinted
by permission from Cell Press:
Immunity
(2002,
16,
77-86)
copyright 2002.
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Secondary reference #1
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Title
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Retinoic acid early inducible genes define a ligand family for the activating nkg2d receptor in mice.
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Authors
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A.Cerwenka,
A.B.Bakker,
T.Mcclanahan,
J.Wagner,
J.Wu,
J.H.Phillips,
L.L.Lanier.
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Ref.
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Immunity, 2000,
12,
721-727.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2. RAE-1 α, β, γ, δ, and H60 Are Ligands for
mNKG2DBa/F3 were transduced with ecotropic retroviruses encoding
RAE-1α, RAE-1β, RAE-1γ, RAE-1δ, and H60. Transduced cells
were sorted by flow cytometry for high expression of mNKG2D
ligands and stained with mNKG2D-Ig FP (filled histograms) or the
control human Ig (open histograms), followed by a biotinylated
anti-human Ig and streptavidin-PE. Data displayed are
representative of results obtained in three independent
experiments.
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Figure 3.
Figure 3. Alignment of RAE-1 α, β, γ, δAlignment of the
predicted amino acid sequences of the RAE-1 α, β, γ, δ
polypeptides. Sites where amino acids differ are denoted by an
asterisk. Potential sites of N-linked glycosylation are
indicated (CHO). “CHO#” designates a potential glycosylation
site that is absent in the RAE-1δ isoform. The predicted sites
of cleavage of the leader segments, the STP-rich domains, and
for the predicted sites for the addition of GPI (caret) are
noted. The sequence of RAE-1δ is deposited as GenBank AF257520.
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The above figures are
reproduced from the cited reference
with permission from Cell Press
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Secondary reference #2
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Title
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Ligands for the murine nkg2d receptor: expression by tumor cells and activation of nk cells and macrophages.
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Authors
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A.Diefenbach,
A.M.Jamieson,
S.D.Liu,
N.Shastri,
D.H.Raulet.
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Ref.
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Nat Immunol, 2000,
1,
119-126.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2. BALB/c thymocytes and stimulated splenocytes express
ligands for mNKG2D. (a) Freshly isolated thymocytes from
C57BL/6 and BALB/c mice were stained with monoclonal antibodies
to CD4 and CD8 and with the streptavidin-phycoerythrin (PE)
-complexed NKG2D tetramer (filled histogram). Staining with an
irrelevant T22-tetramer (solid line) and blocking of the
NKG2D-tetramer staining (dashed line) with an excess (molar
ratio 5:1) of unlabeled tetramer (multimerized with streptavidin
alone) was performed to show the specificity of the staining.
The histograms show electronic gating on the designated cell
populations. One representative experiment out of three is
shown. (b) Splenocytes from C57BL/6 and BALB/c mice were
stimulated for 72 h with ConA or LPS and stained with monoclonal
antibodies to CD4, CD8 and CD19 and with streptavidin-PE
-complexed NKG2D tetramer (filled histogram). Staining with an
irrelevant T22-tetramer (solid line) and blocking of the
NKG2D-tetramer staining (dashed line) with an excess (molar
ratio 5:1) of unlabelled tetramer (multimerized with
streptavidin alone) was performed to show the specificity of the
staining. The histograms show electronic gating on the
designated cell populations. One representative experiment out
of four similar experiments is shown.
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Figure 5.
Figure 5. NKG2D mRNA is expressed in nave NK cells, activated
CD8^ + T cells and LPS-stimulated macrophages.
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The above figures are
reproduced from the cited reference
with permission from Macmillan Publishers Ltd
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