5NB8

Structure of vWC domain from CCN3

5NB8 の概要

• エントリーDOI: 10.2210/pdb5nb8/pdb
• 分子名称: Protein NOV homolog, IMIDAZOLE, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: ccn3, vwc, domains, signalling, bmp, signaling protein
• 由来する生物種: Rattus norvegicus (Rat)
• 細胞内の位置: Secreted : Q9QZQ5
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 42224.98

構造登録者

Xu, E.-R.,Hyvonen, M. (登録日: 2017-03-01, 公開日: 2017-06-14, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.1 Å)