1. Crystal Structure Analysis Reveals How the Chordin Family Member Crossveinless 2 Blocks BMP-2 Receptor Binding
- Author
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Stella E. Weidauer, Matthias Hammerschmidt, Jin-Li Zhang, Alexander Kotzsch, Lucy Patterson, Walter Sebald, Li-Yan Qiu, and Thomas D. Mueller
- Subjects
Genetics ,animal structures ,PROTEINS ,Cell Biology ,Crystal structure ,Biology ,Crossveinless-2 ,Bone morphogenetic protein 2 ,General Biochemistry, Genetics and Molecular Biology ,Cell biology ,Von Willebrand factor ,SIGNALING ,In vivo ,embryonic structures ,Extracellular ,biology.protein ,Chordin ,Receptor ,Molecular Biology ,Developmental Biology - Abstract
SummaryCrossveinless 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.
- Published
- 2008
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