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PDBsum entry 1n3y
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Cell adhesion
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PDB id
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1n3y
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Contents |
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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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Structure and allosteric regulation of the alpha X beta 2 integrin i domain.
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Authors
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T.Vorup-Jensen,
C.Ostermeier,
M.Shimaoka,
U.Hommel,
T.A.Springer.
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Ref.
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Proc Natl Acad Sci U S A, 2003,
100,
1873-1878.
[DOI no: ]
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PubMed id
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Abstract
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The integrin alpha X beta 2 (CD11c/CD18, p150,95) binds ligands through the I
domain of the alpha X subunit. Ligands include the complement factor fragment
iC3b, a key component in the innate immune defense, which, together with the
expression of alpha X beta 2 on dendritic cells and on other leukocytes,
suggests a role in the immune response. We now report the structure of the alpha
X I domain resolved at 1.65 A by x-ray crystallography. To analyze structural
requirements for ligand binding we made a mutation in the alpha X I domain
C-terminal helix, which increased the affinity for iC3b approximately 200-fold
to 2.4 microM compared with the wild-type domain affinity of approximately 400
microM. Gel permeation chromatography supported a conformational change between
the wild-type and mutated domains. Conservation of allosteric regulation in the
alpha X I domain points to the functional importance of this phenomenon.
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Figure 1.
Fig. 1. The  X I domain
structure and comparison to the M I domain.
(A-D) Comparison of X (cyan)
and the M (magenta)
I domains. The MIDAS metal ion present only in M is shown
as a magenta sphere, and the water molecule oxygen present only
in the X MIDAS is
shown as a cyan sphere. (A) Backbones of X and M. (B)
MIDAS region of the X and M I
domains. Residue numbers refer to the X sequence.
(C) Residues in proximity of the X and M MIDAS,
which form part of a putative ligand-binding interface and
differ in structure or polarity between the two I domains ( X and M residues
are labeled in roman and italics, respectively). (D) Detail of
the region forming the hydrophobic socket for Ile-314 ( X) or
Ile-316 ( M). Residue
numbers refer to the X sequence,
and Leu-164 of M is
labeled in italics. All figures were made with RIBBONS software
(41). (E and F) Electrostatic surfaces of the M and X I
domains. The molecular surfaces of the domains were constructed
with GRASP (42). The electrostatic potentials were calculated
with the Delphi algorithm (43) and mapped onto the molecular
surfaces on a scale from  10 kT/e^
 (red)
to +10 kT/e^ (blue).
A Mg2+ ion was placed at the X I domain
MIDAS to make the electrostatic surfaces comparable. Positions
of the metal ions in the X and M I domains
are indicated with arrows.
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Figure 2.
Fig. 2. Comparisons among closed I domain structures of
the C-terminal  -strand and
-helix and
overall secondary structure. (A) The C-terminal 6-strand and
7-helix.
Superposition is based on the entire domain. The backbone
segments shown are X, residues
288-317; M, residues
290-318 of 1JLM (15); 2, residues
306-334 of 1AOX (14); and L, residues
280-308 of 1LFA (16). The side chains of Ile-332 in 2, Ile-316
in M, Ile-314
in X, and
Ile-306 in L are
shown. (B) Structure-based sequence alignment of the X, M, L, and 2 I
domains. The same closed structures as above were superimposed.
[402]alpha -Helices are shown in gold and [403]beta -strands are
shown in cyan. Secondary structure assignment was by the DSSP
algorithm (44) from the structural coordinates.
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