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PDBsum entry 1m1x
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Cell adhesion
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PDB id
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1m1x
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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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Crystal structure of the extracellular segment of integrin alpha vbeta3 in complex with an arg-Gly-Asp ligand.
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Authors
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J.P.Xiong,
T.Stehle,
R.Zhang,
A.Joachimiak,
M.Frech,
S.L.Goodman,
M.A.Arnaout.
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Ref.
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Science, 2002,
296,
151-155.
[DOI no: ]
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PubMed id
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Abstract
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The structural basis for the divalent cation-dependent binding of heterodimeric
alphabeta integrins to their ligands, which contain the prototypical Arg-Gly-Asp
sequence, is unknown. Interaction with ligands triggers tertiary and quaternary
structural rearrangements in integrins that are needed for cell signaling. Here
we report the crystal structure of the extracellular segment of integrin
alphaVbeta3 in complex with a cyclic peptide presenting the Arg-Gly-Asp
sequence. The ligand binds at the major interface between the alphaV and beta3
subunits and makes extensive contacts with both. Both tertiary and quaternary
changes are observed in the presence of ligand. The tertiary rearrangements take
place in betaA, the ligand-binding domain of beta3; in the complex, betaA
acquires two cations, one of which contacts the ligand Asp directly and the
other stabilizes the ligand-binding surface. Ligand binding induces small
changes in the orientation of alphaV relative to beta3.
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Figure 2.
Fig. 2. The ligand-integrin binding site. (A) Surface
representation of the ligand-binding site, with the ligand
peptide shown as ball-and-stick model. Color code for the ligand
and the two visible Mn2+ ions (MIDAS and ADMIDAS) is as in Fig.
1. (B) Interactions between ligand and integrin. The peptide
(yellow) and residues interacting with the ligand or with Mn2+
ions are shown in ball-and-stick representation.  V and  3 residues
are labeled blue and red, respectively. Oxygen and nitrogen
atoms are in red and blue, respectively. The three Mn2+ ions in
3 at MIDAS,
ADMIDAS, and LIMBS are also shown. Hydrogen bonds and salt
bridges (distance cutoff, 3.5 Å) are represented with
dotted lines.
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Figure 3.
Fig. 3. Diagram of the MIDAS motif in A (A and B)
and A from
CD11b (C and D). (A) and (B) MIDAS residues (single letter
abbreviations: S, Ser; E, Glu; D, Asp; T, Thr) in unliganded (A)
and liganded (B) A.
Coordinating side chains are shown in ball-and-stick
representations with oxygen atoms in red, carbon in green; the
ligand aspartate is in gold. In addition to the ligand
aspartate, the Mn2+ (cyan) in the A MIDAS is
coordinated directly with the hydroxyl oxygens of Ser121 and
Ser123 and with one carboxylate oxygen from Glu220. The carboxyl
oxygens of Asp119 and Asp251 of A lie
within 6Å of the metal ion and likely mediate additional
contacts through water molecules similar to the liganded forms
of A (D). The
Mn2+ ion at ADMIDAS (magenta) is present in (A) and (B). The
Mn2+ ions at MIDAS and at LIMBS (cyan and gray, respectively)
are only present in (B). (C) and (D) MIDAS residues in
unliganded (C) and liganded (D) A from
CD11b. The metal ion (cyan) is present in both. Water molecules
are labeled  ; the
pseudoligand glutamate is in gold. Hydrogen bonds and metal ion
coordination are represented with dotted yellow lines.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2002,
296,
151-155)
copyright 2002.
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