5NIR

Crystal structure of collagen 2A vWC domain

Summary for 5NIR

• Entry DOI: 10.2210/pdb5nir/pdb
• Descriptor: Collagen alpha-1(II) chain, 1,2-ETHANEDIOL, DI(HYDROXYETHYL)ETHER, ... (6 entities in total)
• Functional Keywords: collagen, vwc, ecm, bmp-2, structural protein
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted, extracellular space, extracellular matrix : P02458
• Total number of polymer chains: 2
• Total formula weight: 18574.97

Authors

Fischer, G.,Blythe, E.,Hyvonen, M. (deposition date: 2017-03-27, release date: 2017-06-14, Last modification date: 2017-08-09)

Primary citation

Xu, E.R.,Blythe, E.E.,Fischer, G.,Hyvonen, M.
Structural analyses of von Willebrand factor C domains of collagen 2A and CCN3 reveal an alternative mode of binding to bone morphogenetic protein-2.
J. Biol. Chem., 292:12516-12527, 2017

PubMed Abstract: 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.

PubMed: 28584056
DOI: 10.1074/jbc.M117.788992

Experimental method

X-RAY DIFFRACTION (1.74 Å)