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| | <StructureSection load='6maa' size='340' side='right'caption='[[6maa]], [[Resolution|resolution]] 1.39Å' scene=''> | | <StructureSection load='6maa' size='340' side='right'caption='[[6maa]], [[Resolution|resolution]] 1.39Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6maa]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MAA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MAA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6maa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MAA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MAA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.394Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Wfikkn2, Gasp1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6maa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6maa OCA], [http://pdbe.org/6maa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6maa RCSB], [http://www.ebi.ac.uk/pdbsum/6maa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6maa ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6maa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6maa OCA], [https://pdbe.org/6maa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6maa RCSB], [https://www.ebi.ac.uk/pdbsum/6maa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6maa ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/WFKN2_MOUSE 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. | + | [https://www.uniprot.org/uniprot/WFKN2_MOUSE 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: McCoy, J C]] | + | [[Category: McCoy JC]] |
| - | [[Category: Thomas, T B]] | + | [[Category: Thomas TB]] |
| - | [[Category: Walker, R G]] | + | [[Category: Walker RG]] |
| - | [[Category: Follsitatin]]
| + | |
| - | [[Category: Gasp]]
| + | |
| - | [[Category: Kazal]]
| + | |
| - | [[Category: Peptide binding protein]]
| + | |
| - | [[Category: Wfikkn2]]
| + | |
| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ McCoy JC, Walker RG, Murray NH, Thompson TB. Crystal structure of the WFIKKN2 follistatin domain reveals insight into how it inhibits growth differentiation factor 8 (GDF8) and GDF11. J Biol Chem. 2019 Feb 27. pii: RA118.005831. doi: 10.1074/jbc.RA118.005831. PMID:30814254 doi:http://dx.doi.org/10.1074/jbc.RA118.005831
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