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PDBsum entry 1bhq
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Cell adhesion
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PDB id
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1bhq
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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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Cation binding to the integrin cd11b i domain and activation model assessment.
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Authors
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E.T.Baldwin,
R.W.Sarver,
G.L.Bryant,
K.A.Curry,
M.B.Fairbanks,
B.C.Finzel,
R.L.Garlick,
R.L.Heinrikson,
N.C.Horton,
L.L.Kelley,
A.M.Mildner,
J.B.Moon,
J.E.Mott,
V.T.Mutchler,
C.S.Tomich,
K.D.Watenpaugh,
V.H.Wiley.
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Ref.
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Structure, 1998,
6,
923-935.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: The integrin family of cell-surface receptors mediate cell adhesion
through interactions with the extracellular matrix or other cell-surface
receptors. The alpha chain of some integrin heterodimers includes an inserted 'I
domain' of about 200 amino acids which binds divalent metal ions and is
essential for integrin function. Lee et al. proposed that the I domain of the
integrin CD11b adopts a unique 'active' conformation when bound to its counter
receptor. In addition, they proposed that the lack of adhesion in the presence
of Ca2+ ion reflected the stabilization of an 'inactive' I-domain conformation.
We set out to independently determine the structure of the CD11 b I domain and
to evaluate the structural effects of divalent ion binding to this protein.
RESULTS: We have determined the X-ray structure of a new crystal form of the
CD11 b I domain in the absence of added metal ions by multiple isomorphous
replacement (MIR). Metal ions were easily introduced into this crystal form
allowing the straight-forward assessment of the structural effects of divalent
cation binding at the metal ion dependent adhesion site (MIDAS). The equilibrium
binding constants for these ions were determined by titration calorimetry. The
overall protein conformation and metal-ion coordination of the I domain is the
same as that observed for all previously reported CD11 a I-domain structures and
a CD11 b I-domain complex with Mn2+. These structures define a majority
conformation. CONCLUSIONS: Addition of the cations Mg2+, Mn2+ and Cd2+ to the
metal-free I domain does not induce conformational changes in the crystalline
environment. Moreover, we find that Ca2+ binds poorly to the I domain which
serves to explain its failure to support adhesion. We show that the active
conformation proposed by Lee et al, is likely to be a construct artifact and we
propose that the currently available data do not support a dramatic structural
transition for the I domain during counter-receptor binding.
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Figure 1.
Figure 1. I domain secondary structure and conformational
comparison. (a) Ribbon diagram of the CD11b I domain with Mg2+
ion bound at the C-terminal end of the mostly parallel b sheet
(green). The seven a helices are shown in red. The Mg2+ ion
(pink sphere) is coordinated by the conserved residues Ser142,
Ser144 and Asp242, which are shown in ball-and-stick
representation. (b) Superimposed ribbon diagrams of the majority
conformation of the CD11b I domain (red) and the 1ido crystal
structure (green). The different positions of Phe275 and Phe302
(ball-and-stick representation) are indicated. The Mg2+ ions are
indicated by the pink and green spheres. (The figures were
prepared using MOLSCRIPT [82] and rendered using RASTER3D [83].)
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1998,
6,
923-935)
copyright 1998.
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