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PDBsum entry 1uzj
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Matrix protein
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PDB id
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1uzj
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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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Structure of the integrin binding fragment from fibrillin-1 gives new insights into microfibril organization.
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Authors
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S.S.Lee,
V.Knott,
J.Jovanović,
K.Harlos,
J.M.Grimes,
L.Choulier,
H.J.Mardon,
D.I.Stuart,
P.A.Handford.
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Ref.
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Structure, 2004,
12,
717-729.
[DOI no: ]
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PubMed id
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Abstract
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Human fibrillin-1, the major structural protein of extracellular matrix (ECM)
10-12 nm microfibrils, is dominated by 43 calcium binding epidermal growth
factor-like (cbEGF) and 7 transforming growth factor beta binding protein-like
(TB) domains. Crystal structures reveal the integrin binding cbEGF22-TB4-cbEGF23
fragment of human fibrillin-1 to be a Ca(2+)-rigidified tetragonal pyramid. We
suggest that other cbEGF-TB pairs within the fibrillins may adopt a similar
orientation to cbEGF22-TB4. In addition, we have located a flexible RGD integrin
binding loop within TB4. Modeling, cell attachment and spreading assays,
immunocytochemistry, and surface plasmon resonance indicate that cbEGF22 bound
to TB4 is a requirement for integrin activation and provide insight into the
molecular basis of the fibrillin-1 interaction with alphaVbeta3. In light of our
data, we propose a novel model for the assembly of the fibrillin microfibril and
a mechanism to explain its extensibility.
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Figure 6.
Figure 6. Models of Fibrillin-1 and Microfibril
Organization(A) Homology model for cbEGF11-TB5. cbEGF and TB
domains are colored green and blue, respectively. The crystal
structure of cbEGF22-TB4-cbEGF23 fragment is highlighted in
bold. Ca^2+ and potential N-linked glycosylation sites are
represented by red and black spheres, respectively. The RGD
motif on the TB4 loop is indicated.(B) A simple model of the
fibrillin microfibril. The arrows represent fibrillin-1
molecules with dimensions based on the knowledge of the
component domains. The intermolecular transglutaminase
cross-links are shown as X and the associated protein MAGP-1 as
a turquoise diamond. A sketch of the STEM data of Baldock et al.
(2001) is shown below. The colored regions mark the sites of
known antibody epitopes (red, 2502; green, 11C1.3; purple, PF2;
yellow, 2499). The bead regions are shown as gray ellipses.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2004,
12,
717-729)
copyright 2004.
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