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PDBsum entry 1p4l
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Immune system
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PDB id
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1p4l
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Contents |
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273 a.a.
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99 a.a.
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122 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Variable mhc class i engagement by ly49 natural killer cell receptors demonstrated by the crystal structure of ly49c bound to h-2k(b).
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Authors
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J.Dam,
R.Guan,
K.Natarajan,
N.Dimasi,
L.K.Chlewicki,
D.M.Kranz,
P.Schuck,
D.H.Margulies,
R.A.Mariuzza.
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Ref.
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Nat Immunol, 2003,
4,
1213-1222.
[DOI no: ]
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PubMed id
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Abstract
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The Ly49 family of natural killer (NK) receptors regulates NK cell function by
sensing major histocompatibility complex (MHC) class I. Ly49 receptors show
complex patterns of MHC class I cross-reactivity and, in certain cases, peptide
selectivity. To investigate whether specificity differences result from
topological differences in MHC class I engagement, we determined the structure
of the peptide-selective receptor Ly49C in complex with H-2K(b). The Ly49C
homodimer binds two MHC class I molecules in symmetrical way, a mode distinct
from that of Ly49A, which binds MHC class I asymmetrically. Ly49C does not
directly contact the MHC-bound peptide. In addition, MHC crosslinking by Ly49C
was demonstrated in solution. We propose a dynamic model for Ly49-MHC class I
interactions involving conformational changes in the receptor, whereby
variations in Ly49 dimerization mediate different MHC-binding modes.
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Figure 2.
Figure 2. Structure of Ly49/MHC class I complexes. (a)
Superposition of wild-type (blue) and mutant (red) Ly49C -H-2Kb
complexes in the crystallographic asymmetric unit, indicating
close overall similarity. (b) Electron density in the interface
of the mutant Ly49C -H-2Kb complex. The F[o] - F[c] omit map at
2.9 Å resolution is contoured at 2.5  .
Ly49C residues 239 -243 (red), H-2Kb heavy chain residues 111
-117 (blue) and  [2]M
residues 58 -60 (yellow) were excluded from the map calculation.
(c) Ribbon diagram of the mutant Ly49C -H-2Kb complex, in which
the crystallographic Ly49C dimer (red) crosslinks two MHC class
I molecules. (d) Structure of the Ly49A -H-2D^d complex, showing
the asymmetric interaction between the Ly49A dimer (green) and
two MHC class I molecules. The two interaction surfaces, site 1
and site 2, are indicated by the dashed circle and rectangle,
respectively. In c and d, the H-2Kb heavy chain is blue, the
ovalbumin peptide (ball-and-stick representation) is red and
[2]M
is yellow.
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Figure 6.
Figure 6. Comparison of hydrogen-bonding networks at the Ly49C
-H-2Kb and Ly49A -H-2D^d interfaces. (a) Detailed view
(stereo diagram) of the Ly49C -H-2Kb interface showing hydrogen
bonds (dotted black lines) between Ly49C (red) and the H-2Kb
heavy chain (blue) or [2]M
(violet); the side chains of interacting residues are yellow.
The portion of the Ly49C L3 loop, encompassing residues 226
-231, which is disordered in both mutant and wild-type
structures, is drawn arbitrarily (red balls). With the exception
of H-2Kb residues Asp212 and Thr214, whose side chains could
potentially interact with the disordered L3 loop of Ly49C, only
residues forming hydrogen bonds are shown. (b) Stereo diagram
showing hydrogen bonds between Ly49A (green) and the H-2D^d
heavy chain (blue) or [2]M
(violet) at the site 2 interface of the Ly49A -H-2D^d complex.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Immunol
(2003,
4,
1213-1222)
copyright 2003.
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