6maa

WFIKKN2 Follistatin Domain

spinqualitylabelsall models 6maa, resolution 1.39Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6maa is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.394Å Ligands: NO3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function WFKN2_MOUSE Protease-inhibitor that contains multiple distinct protease inhibitor domains. Probably has serine protease- and metalloprotease-inhibitor activity (By similarity). Inhibits the biological activity of mature myostatin, but not activin. Publication Abstract from PubMed Growth differentiation factor 8 (GDF8), a.k.a. myostatin, and GDF11 are closely related members of the transforming growth factor beta (TGF-beta) family. GDF8 strongly and negatively regulates skeletal muscle growth, and GDF11 has been implicated in various age-related pathologies such as cardiac hypertrophy. GDF8 and GDF11 signaling activities are controlled by the extracellular protein antagonists follistatin, follistatin-like 3 (FSTL3), and WAP, follistatin/kazal, immunoglobulin, Kunitz and netrin domain containing (WFIKKN). All of these proteins contain a follistatin domain (FSD) important for ligand binding and antagonism. Here, we investigated the structure and function of the FSD from murine WFIKKN2 and compared it with the FSDs of follistatin and FSTL3. Using native gel shift and surface plasmon resonance analyses, we determined that the WFIKKN2 FSD can interact with both GDF8 and GDF11 and block their interactions with the type II receptor activin A receptor type 2B (ActRIIB). Further, we solved the crystal structure of the WFIKKN2 FSD to 1.39 A resolution and identified surface-exposed residues that when substituted with alanine, reduce antagonism of GDF8 in full-length WFIKKN2. Comparison of the WFIKKN2 FSD with those of follistatin and FSTL3 revealed differences in both the FSD structure and position of residues within the domain that are important for ligand antagonism. Taken together, our results indicate that both WFIKKN and follistatin utilize their FSDs to block the type II receptor but do so via different binding interactions. Crystal structure of the WFIKKN2 follistatin domain reveals insight into how it inhibits growth differentiation factor 8 (GDF8) and GDF11.,McCoy JC, Walker RG, Murray NH, Thompson TB J Biol Chem. 2019 Feb 27. pii: RA118.005831. doi: 10.1074/jbc.RA118.005831. PMID:30814254 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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