3BK3

Crystal structure of the complex of BMP-2 and the first Von Willebrand domain type C of Crossveinless-2

Summary for 3BK3

• Entry DOI: 10.2210/pdb3bk3/pdb
• Related: 1REW 2H62 2H64
• Descriptor: Bone morphogenetic protein 2, Crossveinless 2 (3 entities in total)
• Functional Keywords: tgf-beta superfamily, bmp modulator proteins, chordin, bmp inhibitor, chondrogenesis, cleavage on pair of basic residues, cytokine, developmental protein, differentiation, glycoprotein, growth factor, osteogenesis, polymorphism, secreted, hormone-growth factor complex, hormone/growth factor
• Biological source: Homo sapiens (Human); More
• Cellular location: Secreted: P12643
• Total number of polymer chains: 4
• Total formula weight: 40136.38

Authors

Mueller, T.D.,Sebald, W.,Zhang, J.-L. (deposition date: 2007-12-05, release date: 2008-05-27, Last modification date: 2024-10-16)

Primary citation

Zhang, J.-L.,Qiu, L.-Y.,Kotzsch, A.,Weidauer, S.,Patterson, L.,Hammerschmidt, M.,Sebald, W.,Mueller, T.D.
Crystal structure analysis reveals how the Chordin family member crossveinless 2 blocks BMP-2 receptor binding
Dev.Cell, 14:739-750, 2008

PubMed Abstract: 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.

PubMed: 18477456
DOI: 10.1016/j.devcel.2008.02.017

Experimental method

X-RAY DIFFRACTION (2.7 Å)