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PDBsum entry 5nir
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Structural protein
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PDB id
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5nir
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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 analyses of von willebrand factor c domains of collagen 2a and ccn3 reveal an alternative mode of binding to bone morphogenetic protein-2.
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Authors
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E.R.Xu,
E.E.Blythe,
G.Fischer,
M.Hyvönen.
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Ref.
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J Biol Chem, 2017,
292,
12516-12527.
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PubMed id
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Abstract
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Bone morphogenetic proteins (BMPs) are secreted growth factors that promote
differentiation processes in embryogenesis and tissue development. Regulation of
BMP signaling involves binding to a variety of extracellular proteins, among
which are many von Willebrand factor C (vWC) domain-containing proteins.
Although the crystal structure of the complex of crossveinless-2 (CV-2) vWC1 and
BMP-2 previously revealed one mode of the vWC/BMP-binding mechanism, other vWC
domains may bind to BMP differently. Here, using X-ray crystallography, we
present for the first time structures of the vWC domains of two proteins thought
to interact with BMP-2: collagen IIA and matricellular protein CCN3. We found
that these two vWC domains share a similar N-terminal fold that differs greatly
from that in CV-2 vWC, which comprises its BMP-2-binding site. We analyzed the
ability of these vWC domains to directly bind to BMP-2 and detected an
interaction only between the collagen IIa vWC and BMP-2. Guided by the collagen
IIa vWC domain crystal structure and conservation of surface residues among
orthologous domains, we mapped the BMP-binding epitope on the subdomain 1 of the
vWC domain. This binding site is different from that previously observed in the
complex between CV-2 vWC and BMP-2, revealing an alternative mode of interaction
between vWC domains and BMPs.
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