5hk5

Structure of the Grem2-GDF5 Inhibitory Complex

spinqualitylabelsall models 5hk5, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5hk5 is a 8 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.9Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GREM2_MOUSE Cytokine that inhibits the activity of BMP2 and BMP4 in a dose-dependent manner. Antagonized BMP4-induced suppression of progesterone production in granulosa cells. Publication Abstract from PubMed The DAN family, including Gremlin-1 and Gremlin-2 (Grem1 and Grem2), represents a large family of secreted BMP (bone morphogenetic protein) antagonists. However, how DAN proteins specifically inhibit BMP signaling has remained elusive. Here, we report the structure of Grem2 bound to GDF5 at 2.9-A resolution. The structure reveals two Grem2 dimers binding perpendicularly to each GDF5 monomer, resembling an H-like structure. Comparison to the unbound Grem2 structure reveals a dynamic N terminus that undergoes significant transition upon complex formation, leading to simultaneous interaction with the type I and type II receptor motifs on GDF5. Binding studies show that DAN-family members can interact with BMP-type I receptor complexes, whereas Noggin outcompetes the type I receptor for ligand binding. Interestingly, Grem2-GDF5 forms a stable aggregate-like structure in vitro that is not clearly observed for other antagonists, including Noggin and Follistatin. These findings exemplify the structural and functional diversity across the various BMP antagonist families. Structure of Gremlin-2 in Complex with GDF5 Gives Insight into DAN-Family-Mediated BMP Antagonism.,Nolan K, Kattamuri C, Rankin SA, Read RJ, Zorn AM, Thompson TB Cell Rep. 2016 Aug 23;16(8):2077-86. doi: 10.1016/j.celrep.2016.07.046. Epub 2016, Aug 11. PMID:27524626 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Growth differentiation factor 3D STRUCTURES

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