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PDBsum entry 2vkx
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Cell adhesion
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PDB id
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2vkx
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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 of the tandem fibronectin type 3 domains of neural cell adhesion molecule.
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Authors
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F.Carafoli,
J.L.Saffell,
E.Hohenester.
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Ref.
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J Mol Biol, 2008,
377,
524-534.
[DOI no: ]
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PubMed id
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Abstract
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Activation of the fibroblast growth factor receptor (FGFR) by neural cell
adhesion molecule (NCAM) is essential for NCAM-mediated neurite outgrowth.
Previous peptide studies have identified two regions in the fibronectin type 3
(FN3)-like domains of NCAM as being important for these activities. Here we
report the crystal structure of the NCAM FN3 domain tandem, which reveals an
acutely bent domain arrangement. Mutation of a non-conserved surface residue
(M610R) led to a second crystal form showing a substantially different
conformation. Thus, the FN3 domain linker is highly flexible, suggesting that it
corresponds to the hinge seen in electron micrographs of NCAM. The two putative
FGFR1-binding segments, one in each NCAM FN3 domain, are situated close to the
domain interface. They form a contiguous patch in the more severely bent
conformation but become separated upon straightening of the FN3 tandem,
suggesting that conformational changes within NCAM may modulate FGFR1
activation. Surface plasmon resonance experiments demonstrated only a very weak
interaction between the NCAM FN3 tandem and soluble FGFR1 proteins expressed in
mammalian cells (dissociation constant >100 muM). Thus, the NCAM-FGFR1
interaction at the cell surface is likely to depend upon avidity effects due to
receptor clustering.
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Figure 3.
Fig. 3. Structure of M610R mutant. (a) C^α trace of the
structure of the NCAM ^1FN3–^2FN3 M610R mutant, viewed along
the 3-fold non-crystallographic symmetry axis. One molecule is
highlighted in yellow (^1FN3 domain) and brown (^2FN3 domains).
(b) Superposition of the FN3 pairs of wild-type NCAM (cyan),
NCAM M610R mutant (green) and neuroglian (magenta).^37 The
structures were superimposed on the conserved β-strands of the
second FN3 domain. wt indicates wild type.
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Figure 4.
Fig. 4. Location of putative FGFR1 binding site. Shown are
surface representations of (a) wild-type NCAM ^1FN3–^2FN3 and
(b) its M610R mutant. The FRM and FGL sequences (see the text)
are shown in red and yellow, respectively.
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The above figures are
reprinted
from an Open Access publication published by Elsevier:
J Mol Biol
(2008,
377,
524-534)
copyright 2008.
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