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PDBsum entry 3bn3
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Cell adhesion, immune system
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PDB id
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3bn3
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References listed in PDB file
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Key reference
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Title
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An unusual allosteric mobility of the c-Terminal helix of a high-Affinity alphal integrin i domain variant bound to icam-5.
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Authors
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H.Zhang,
J.M.Casasnovas,
M.Jin,
J.H.Liu,
C.G.Gahmberg,
T.A.Springer,
J.H.Wang.
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Ref.
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Mol Cell, 2008,
31,
432-437.
[DOI no: ]
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PubMed id
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Abstract
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Integrins are cell surface receptors that transduce signals bidirectionally
across the plasma membrane. The key event of integrin signaling is the
allosteric regulation between its ligand-binding site and the C-terminal helix
(alpha7) of integrin's inserted (I) domain. A significant axial movement of the
alpha7 helix is associated with the open, active conformation of integrins. We
describe the crystal structure of an engineered high-affinity I domain from the
integrin alpha(L)beta(2) (LFA-1) alpha subunit in complex with the N-terminal
two domains of ICAM-5, an adhesion molecule expressed in telencephalic neurons.
The finding that the alpha7 helix swings out and inserts into a neighboring I
domain in an upside-down orientation in the crystals implies an intrinsically
unusual mobility of this helix. This remarkable feature allows the alpha7 helix
to trigger integrin's large-scale conformational changes with little energy
penalty. It serves as a mechanistic example of how a weakly bound adhesion
molecule works in signaling.
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Figure 1.
Figure 1. Ribbon Diagram of the ICAM-5/dm-I Complex
Two
symmetry-related complexes of the ICAM-5/dm-I domain are shown.
In one complex ICAM-5 is in cyan and the I domain in green. In
the other complex the I domain is in magenta and the ICAM-5
molecule is in shadow for clarity. The C-terminal α7 helix of
the magenta I domain inserts into a groove in the green I domain
in an upside-down fashion. Glu-37 in ICAM-5 D1 that binds to the
I domain's MIDAS is shown in red as a ball-and-stick model. The
figures are all prepared with Pymol (http://www.pymol.org/).
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Figure 2.
Figure 2. Superimposition of the ICAM-3/HA Complex onto the
ICAM-5/dm-I Complex
ICAM-3/HA is in red and the ICAM-5/dm-I
complex is in cyan. For clarity, the ICAM-5 D2 is not shown in
the figures. The conserved Glu-37 is in yellow.
(A) The
superposition is based on I domains. Side chains at the two
mutation sites are shown in a ball-and-stick model with Phe265
and Phe292 in the HA replaced by Ser265 and Gly292 in the dm-I
domain, respectively. Also shown are Leu289s where the
polypeptide chains of the two I domains start to run opposite
directions.
(B) The ICAMs' domain D1s were used for
superposition. HA I domain from the ICAM-3/HA complex is not
shown for clarity. The loops of R41-T45 in ICAM-5 and S41-V45 in
ICAM-3 are colored green and magenta, respectively. Residue N43
and attached sugar NAG-2 from ICAM-5 D1 are also shown as a
ball-and-stick model.
(C) The stereo view of the local
region around MIDAS of superimposed I domains. The I domain from
ICAM-5 complex is in green, that from the ICAM-3 complex is in
cyan, and the closed form of the α[L] I domain (1ZOP) in
magenta. Glu-37 from ICAM-5 that binds to MIDAS is shown in
yellow. The metal ion is shown as a ball. Side chains of
residues D239, S265, F265, and G262 are labeled and shown in a
ball-and-stick model. The yellow arrows indicate the movement
direction of the β4α5 loop and the F265 ring from closed form
to open form.
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The above figures are
reprinted
from an Open Access publication published by Cell Press:
Mol Cell
(2008,
31,
432-437)
copyright 2008.
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