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PDBsum entry 3c8k
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Immune system
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PDB id
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3c8k
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Contents |
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274 a.a.
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99 a.a.
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125 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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Molecular architecture of the major histocompatibility complex class i-Binding site of ly49 natural killer cell receptors.
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Authors
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L.Deng,
S.Cho,
E.L.Malchiodi,
M.C.Kerzic,
J.Dam,
R.A.Mariuzza.
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Ref.
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J Biol Chem, 2008,
283,
16840-16849.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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Natural killer (NK) cells play a vital role in the detection and destruction of
virally infected and tumor cells during innate immune responses. The highly
polymorphic Ly49 family of NK receptors regulates NK cell function by sensing
major histocompatibility complex class I (MHC-I) molecules on target cells.
Despite the determination of two Ly49-MHC-I complex structures, the molecular
features of Ly49 receptors that confer specificity for particular MHC-I alleles
have not been identified. To understand the functional architecture of
Ly49-binding sites, we determined the crystal structures of Ly49C and Ly49G and
completed refinement of the Ly49C-H-2K(b) complex. This information, combined
with mutational analysis of Ly49A, permitted a structure-based classification of
Ly49s that we used to dissect the binding site into three distinct regions, each
having different roles in MHC recognition. One region, located at the center of
the binding site, has a similar structure across the Ly49 family and mediates
conserved interactions with MHC-I that contribute most to binding. However, the
preference of individual Ly49s for particular MHC-I molecules is governed by two
regions that flank the central region and are structurally more variable. One of
the flanking regions divides Ly49s into those that recognize both H-2D and H-2K
versus only H-2D ligands, whereas the other discriminates among H-2D or H-2K
alleles. The modular design of Ly49-binding sites provides a framework for
predicting the MHC-binding specificity of Ly49s that have not been characterized
experimentally.
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Figure 2.
FIGURE 2. Structure of the Ly49C-H-2K^b complex. A, ribbon
diagram of the Ly49C-H-2K^b complex. Domains are labeled. The
 1,
2,
and 3 domains of the MHC-I
heavy chain are green; β[2]mis orange; the MHC-bound peptide in
ball-and-stick representation is gray; the Ly49C dimer is rose.
B, composite omit electron density map (dark green, contoured at
1.5  ) of Ly49C-H-2K^b at
2.90 Å resolution, showing residues 218-226 of Ly49C helix
3.
C, structural rearrangements in Ly49C induced by binding to
MHC-I. Bound Ly49C is rose; unbound Ly49C is gold; H-2K^b is
green. Salt bridges are indicated by solid lines.
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Figure 3.
FIGURE 3. Comparison of Ly49-MHC-I interfaces. A,
Ly49C-H-2K^b interface, highlighting interactions made by
residues 211-231 of Ly49C. B, Ly49A-H-2D^d complex, showing
interactions made by the corresponding region of Ly49A. Domains
are labeled. The side chains of interacting residues are drawn
in ball-and-stick representation, with carbon atoms in rose
(Ly49C), cyan (Ly49A), green (H-2K^b or H-2D^d), or orange
(β[2]m), and oxygen atoms in red, nitrogen atoms in blue, and
sulfur in yellow. Salt bridges and hydrogen bonds are
represented by solid and dotted lines, respectively.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2008,
283,
16840-16849)
copyright 2008.
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