Crystal Structure Analysis Reveals How the Chordin Family Member Crossveinless 2 Blocks BMP-2 Receptor Binding
Copyright policy )Crystal Structure Analysis Reveals How the Chordin Family Member Crossveinless 2 Blocks BMP-2 Receptor Binding
Crossveinless 2 (CV-2) is an extracellular BMP modulator protein belonging to the Chordin family. During development it is expressed at sites of high BMP signaling and like Chordin CV-2 can either enhance or inhibit BMP activity. CV-2 binds to BMP-2 via its N-terminal Von Willebrand factor type C (VWC) domain 1. Here we report the structure of the complex between CV-2 VWC1 and BMP-2. The tripartite VWC1 binds BMP-2 only through a short N-terminal segment, called clip, and subdomain (SD) 1. Mutational analysis establishes that the clip segment and SD1 together create high-affinity BMP-2 binding. All four receptor-binding sites of BMP-2 are blocked in the complex, demonstrating that VWC1 acts as competitive inhibitor for all receptor types. In vivo experiments reveal that the BMP-enhancing (pro-BMP) activity of CV-2 is independent of BMP-2 binding by VWC1, showing that pro- and anti-BMP activities are structurally separated in CV-2.
- Max Planck Society Germany
- University of Würzburg Germany
- University Hospital Würzburg Germany
Models, Molecular, PROTEINS, Molecular Sequence Data, Bone Morphogenetic Protein 2, Bone Morphogenetic Protein Receptors, Type II, Crystallography, X-Ray, Protein Structure, Secondary, Cell Line, Epitopes, Mice, Animals, Amino Acid Sequence, Collagen Type II, Bone Morphogenetic Protein Receptors, Type I, Binding Sites, GTPase-Activating Proteins, Hydrogen Bonding, Fibronectins, SIGNALING, Bone Morphogenetic Proteins, Hydrophobic and Hydrophilic Interactions, Developmental Biology, Protein Binding
Models, Molecular, PROTEINS, Molecular Sequence Data, Bone Morphogenetic Protein 2, Bone Morphogenetic Protein Receptors, Type II, Crystallography, X-Ray, Protein Structure, Secondary, Cell Line, Epitopes, Mice, Animals, Amino Acid Sequence, Collagen Type II, Bone Morphogenetic Protein Receptors, Type I, Binding Sites, GTPase-Activating Proteins, Hydrogen Bonding, Fibronectins, SIGNALING, Bone Morphogenetic Proteins, Hydrophobic and Hydrophilic Interactions, Developmental Biology, Protein Binding
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