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PDBsum entry 2v53
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Cell adhesion
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PDB id
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2v53
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References listed in PDB file
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Key reference
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Title
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Structural basis of sequence-Specific collagen recognition by sparc.
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Authors
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E.Hohenester,
T.Sasaki,
C.Giudici,
R.W.Farndale,
H.P.Bächinger.
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Ref.
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Proc Natl Acad Sci U S A, 2008,
105,
18273-18277.
[DOI no: ]
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PubMed id
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Abstract
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Protein interactions with the collagen triple helix play a critical role in
collagen fibril formation, cell adhesion, and signaling. However, structural
insight into sequence-specific collagen recognition is limited to an
integrin-peptide complex. A GVMGFO motif in fibrillar collagens (O denotes
4-hydroxyproline) binds 3 unrelated proteins: von Willebrand factor (VWF),
discoidin domain receptor 2 (DDR2), and the extracellular matrix protein
SPARC/osteonectin/BM-40. We report the crystal structure at 3.2 A resolution of
human SPARC bound to a triple-helical 33-residue peptide harboring the
promiscuous GVMGFO motif. SPARC recognizes the GVMGFO motifs of the middle and
trailing collagen chains, burying a total of 720 A(2) of solvent-accessible
collagen surface. SPARC binding does not distort the canonical triple helix of
the collagen peptide. In contrast, a critical loop in SPARC is substantially
remodelled upon collagen binding, creating a deep pocket that accommodates the
phenylalanine residue of the trailing collagen chain ("Phe pocket"). This highly
restrictive specificity pocket is shared with the collagen-binding integrin
I-domains but differs strikingly from the shallow collagen-binding grooves of
the platelet receptor glycoprotein VI and microbial adhesins. We speculate that
binding of the GVMGFO motif to VWF and DDR2 also results in structural changes
and the formation of a Phe pocket.
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Figure 1.
Crystal structure of SPARC FS-EC ΔαC bound to a 33-residue
collagen peptide (stereoview). The FS and EC domains of SPARC
are in green and cyan, respectively. Disulphide bridges are in
pale pink, the glycan attached to N99 is in gray, and a calcium
ion is shown as a purple sphere. The collagen peptide is shown
as a Cα ribbon (leading chain, yellow; middle chain, orange;
trailing chain, red). The chain termini, selected helices and
the location of the αC deletion are labeled.
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Figure 4.
Putative SPARC-binding sites in collagen IV. Shown are
partial sequences of human collagen III (SwissProt entry P02461)
and collagen IV (α1 chain, P02462; α2 chain, P08572). The
SPARC-binding site in collagen III is highlighted; residues that
are predicted to be strictly required for SPARC binding (see
Prediction of SPARC-Binding Sites in Collagens I–IV) are in
red, residues that should be apolar are in orange. The same
coloring scheme is used to indicate the 4 putative SPARC-binding
sites in collagen IV.
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Secondary reference #1
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Title
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Crystal structure and mapping by site-Directed mutagenesis of the collagen-Binding epitope of an activated form of bm-40/sparc/osteonectin.
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Authors
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T.Sasaki,
E.Hohenester,
W.Göhring,
R.Timpl.
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Ref.
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Embo J, 1998,
17,
1625-1634.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2 Structure of BM-40  I,
 C.
(A) Two orthogonal views (Kraulis, 1991) related by a rotation
of 90° about the vertical axis. The FS domain is in green and
the EC domain is in red. The calcium ions bound to the EF hand
pair in the EC domain (Ca1 and Ca2) are in yellow; the calcium
ion bound at the tip of the E
- F
loop (Ca3) is in blue. Helices in the EC domain are labelled.
Note that five residues around the deletion site (marked by a
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Figure 3.
Figure 3 Stereo view (Kraulis, 1991) of a C[  ]trace
of the BM-40 I,
C
structure showing the residues that were mutated in this study
(see text). Disulfide bridges are shown with thick bonds.
Mutated residues are identified by position numbers and their
side chains. The three calcium ions are shown as black spheres.
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The above figures are
reproduced from the cited reference
which is an Open Access publication published by Macmillan Publishers Ltd
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