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PDBsum entry 1bmo
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Extracellular module
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PDB id
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1bmo
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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 a pair of follistatin-Like and ef-Hand calcium-Binding domains in bm-40.
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Authors
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E.Hohenester,
P.Maurer,
R.Timpl.
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Ref.
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Embo J, 1997,
16,
3778-3786.
[DOI no: ]
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PubMed id
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Abstract
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BM-40 (also known as SPARC or osteonectin) is an anti-adhesive secreted
glycoprotein involved in tissue remodelling. Apart from an acidic N-terminal
segment, BM-40 consists of a follistatin-like (FS) domain and an EF-hand
calcium-binding (EC) domain. Here we report the crystal structure at 3.1 A
resolution of the FS-EC domain pair of human BM-40. The two distinct domains
interact through a small interface that involves the EF-hand pair of the EC
domain. Residues implicated in cell binding, inhibition of cell spreading and
disassembly of focal adhesions cluster on one face of BM-40, opposite the
binding epitope for collagens and the N-linked carbohydrate. The elongated FS
domain is structurally related to serine protease inhibitors of the Kazal
family. Notable differences are an insertion into the inhibitory loop in BM-40
and a protruding N-terminal beta-hairpin with striking similarities to epidermal
growth factor. This hairpin is likely to act as a rigid spacer in proteins
containing tandemly repeated FS domains, such as follistatin and agrin, and
forms the heparin-binding site in follistatin.
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Figure 1.
Figure 1 Stereo view (Kraulis, 1991) of the BM-40 FS -EC
structure and its secondary structure elements. The FS domain
(residues 54 -137) is shown in green and consists of an
N-terminal  -hairpin
and a small hydrophobic core of  /
structure.
The EC domain (residues 138 -286) is in red and consists of a
pair of EF-hand calcium-binding sites and helices A, B and C.
The calcium ions bound to the EF-hands are shown as yellow
spheres. The FS and EC domains interact through a small
interface involving mainly 5
and the preceding loop of the FS domain and E
of the EC domain. The FS domain is glycosylated at Asn99; the
first two N-acetylglucosamine (NAG) sugar moieties are included
in the crystallographic model and are shown in atomic detail.
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Figure 6.
Figure 6 Model of a tandem of FS domains in follistatin and
agrin. The N-terminal domain (in green) and the C-terminal
domain (in red) are linked by an extended segment of three
residues (in blue); the relative rotation between the two
domains is  0°.
The tip of the N-terminal -hairpin
of the C-terminal domain contacts the N-terminal domain at the
small three-stranded -sheet
and stabilizes the linear arrangement of domains. In this model,
helix 2,
which is unique to BM-40, has been replaced with the
corresponding segment of ovomucoid (compare Figures 3 and 4A).
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
Embo J
(1997,
16,
3778-3786)
copyright 1997.
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Secondary reference #1
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Title
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Structure of a novel extracellular ca(2+)-Binding module in bm-40.
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Authors
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E.Hohenester,
P.Maurer,
C.Hohenadl,
R.Timpl,
J.N.Jansonius,
J.Engel.
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Ref.
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Nat Struct Biol, 1996,
3,
67-73.
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PubMed id
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Secondary reference #2
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Title
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The c-Terminal portion of bm-40 (sparc/osteonectin) is an autonomously folding and crystallisable domain that binds calcium and collagen IV.
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Authors
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P.Maurer,
C.Hohenadl,
E.Hohenester,
W.Göhring,
R.Timpl,
J.Engel.
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Ref.
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J Mol Biol, 1995,
253,
347-357.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2. Overlap plot of sensorgrams of the interaction
of human BM-40 with human collagen IV. The collagen
was immobilized to the sensor chip. Injections (four
minutes) of BM-40 at the concentrations indicated were
done at a flow-rate of 10 ml/minute and then replaced by
buffer solution to monitor dissociation.
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Figure 3.
Figure 3. Circular dichroism spectra of the EF-hand
analog peptide. Far UV spectra were recorded at
a peptide concentration of 0.1 mM in the absence of
Ca
2+
(curve 1), at 0.5 mM Ca
2+
(curve 2), at 50 mM Ca
2+
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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Secondary reference #3
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Title
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The biology of sparc, A protein that modulates cell-Matrix interactions.
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Authors
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T.F.Lane,
E.H.Sage.
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Ref.
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Faseb J, 1994,
8,
163-173.
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PubMed id
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