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| | <StructureSection load='3fg6' size='340' side='right'caption='[[3fg6]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='3fg6' size='340' side='right'caption='[[3fg6]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3fg6]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FG6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FG6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3fg6]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FG6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FG6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1svy|1svy]], [[1h1v|1h1v]], [[1p8x|1p8x]], [[2fh1|2fh1]], [[1d0n|1d0n]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SCIN, KIAA1905 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3fg6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fg6 OCA], [https://pdbe.org/3fg6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fg6 RCSB], [https://www.ebi.ac.uk/pdbsum/3fg6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fg6 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=3fg6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fg6 OCA], [https://pdbe.org/3fg6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fg6 RCSB], [https://www.ebi.ac.uk/pdbsum/3fg6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fg6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ADSV_HUMAN ADSV_HUMAN]] Ca(2+)-dependent actin filament-severing protein that is presumed to have a regulatory function in exocytosis by affecting the organization of the microfilament network underneath the plasma membrane. In vitro, also has barbed end capping and nucleating activities in the presence of Ca(2+). Regulates chondrocyte proliferation and differentiation. MAP kinases p38 and ERK1/2 mediate the adseverin-induced accelerated differentiation of non-hypertrophic chondrocytes (By similarity).
| + | [https://www.uniprot.org/uniprot/SCIN_HUMAN SCIN_HUMAN] Ca(2+)-dependent actin filament-severing protein that has a regulatory function in exocytosis by affecting the organization of the microfilament network underneath the plasma membrane (PubMed:8547642, PubMed:26365202). Severing activity is inhibited by phosphatidylinositol 4,5-bis-phosphate (PIP2) (By similarity). In vitro, also has barbed end capping and nucleating activities in the presence of Ca(2+). Required for megakaryocyte differentiation, maturation, polyploidization and apoptosis with the release of platelet-like particles (PubMed:11568009). Plays a role in osteoclastogenesis (OCG) and actin cytoskeletal organization in osteoclasts (By similarity). Regulates chondrocyte proliferation and differentiation (By similarity). Inhibits cell proliferation and tumorigenesis. Signaling is mediated by MAPK, p38 and JNK pathways (PubMed:11568009).[UniProtKB:Q28046][UniProtKB:Q5ZIV9][UniProtKB:Q60604]<ref>PMID:11568009</ref> <ref>PMID:26365202</ref> <ref>PMID:8547642</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Robinson, R C]] | + | [[Category: Robinson RC]] |
| - | [[Category: Actin capping]]
| + | |
| - | [[Category: Actin-binding]]
| + | |
| - | [[Category: Actin-binding protein]]
| + | |
| - | [[Category: C-terminus of adseverin]]
| + | |
| - | [[Category: Cytoskeleton]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| Structural highlights
Function
SCIN_HUMAN Ca(2+)-dependent actin filament-severing protein that has a regulatory function in exocytosis by affecting the organization of the microfilament network underneath the plasma membrane (PubMed:8547642, PubMed:26365202). Severing activity is inhibited by phosphatidylinositol 4,5-bis-phosphate (PIP2) (By similarity). In vitro, also has barbed end capping and nucleating activities in the presence of Ca(2+). Required for megakaryocyte differentiation, maturation, polyploidization and apoptosis with the release of platelet-like particles (PubMed:11568009). Plays a role in osteoclastogenesis (OCG) and actin cytoskeletal organization in osteoclasts (By similarity). Regulates chondrocyte proliferation and differentiation (By similarity). Inhibits cell proliferation and tumorigenesis. Signaling is mediated by MAPK, p38 and JNK pathways (PubMed:11568009).[UniProtKB:Q28046][UniProtKB:Q5ZIV9][UniProtKB:Q60604][1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Adseverin is a member of the calcium-regulated gelsolin superfamily of actin severing and capping proteins. Adseverin comprises 6 homologous domains (A1-A6), which share 60% identity with the 6 domains from gelsolin (G1-G6). Adseverin is truncated in comparison to gelsolin, lacking the C-terminal extension that masks the F-actin binding site in calcium-free gelsolin. Biochemical assays have indicated differences in the interaction of the C-terminal halves of adseverin and gelsolin with actin. Gelsolin contacts actin through a major site on G4 and a minor site on G6, whereas adseverin uses a site on A5. Here, we present the X-ray structure of the activated C-terminal half of adseverin (A4-A6). This structure is highly similar to that of the activated form of the C-terminal half of gelsolin (G4-G6), both in arrangement of domains and in the 3 bound calcium ions. Comparative analysis of the actin-binding surfaces observed in the G4-G6/actin structure suggests that adseverin in this conformation will also be able to interact with actin through A4 and A6, whereas the A5 surface is obscured. A single residue mutation in A4-A6 located at the predicted A4/actin interface completely abrogates actin sequestration. A model of calcium-free adseverin, constructed from the structure of gelsolin, predicts that in the absence of a gelsolin-like C-terminal extension the interaction between A2 and A6 provides the steric inhibition to prevent interaction with F-actin. We propose that calcium binding to the N terminus of adseverin dominates the activation process to expose the F-actin binding site on A2.
The crystal structure of the C-terminus of adseverin reveals the actin-binding interface.,Chumnarnsilpa S, Lee WL, Nag S, Kannan B, Larsson M, Burtnick LD, Robinson RC Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13719-24. Epub 2009 Aug 4. PMID:19666531[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zunino R, Li Q, Rosé SD, Romero-Benítez MM, Lejen T, Brandan NC, Trifaró JM. Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis. Blood. 2001 Oct 1;98(7):2210-9. PMID:11568009 doi:10.1182/blood.v98.7.2210
- ↑ Chumnarnsilpa S, Robinson RC, Grimes JM, Leyrat C. Calcium-controlled conformational choreography in the N-terminal half of adseverin. Nat Commun. 2015 Sep 14;6:8254. doi: 10.1038/ncomms9254. PMID:26365202 doi:http://dx.doi.org/10.1038/ncomms9254
- ↑ Marcu MG, Zhang L, Nau-Staudt K, Trifaró JM. Recombinant scinderin, an F-actin severing protein, increases calcium-induced release of serotonin from permeabilized platelets, an effect blocked by two scinderin-derived actin-binding peptides and phosphatidylinositol 4,5-bisphosphate. Blood. 1996 Jan 1;87(1):20-4 PMID:8547642
- ↑ Chumnarnsilpa S, Lee WL, Nag S, Kannan B, Larsson M, Burtnick LD, Robinson RC. The crystal structure of the C-terminus of adseverin reveals the actin-binding interface. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13719-24. Epub 2009 Aug 4. PMID:19666531
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