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| | <StructureSection load='5a1k' size='340' side='right'caption='[[5a1k]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='5a1k' size='340' side='right'caption='[[5a1k]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5a1k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5A1K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5A1K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5a1k]] is a 2 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=5A1K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5A1K FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5a1m|5a1m]]</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]] 2.9Å</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=5a1k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5a1k OCA], [http://pdbe.org/5a1k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5a1k RCSB], [http://www.ebi.ac.uk/pdbsum/5a1k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5a1k 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=5a1k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5a1k OCA], [https://pdbe.org/5a1k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5a1k RCSB], [https://www.ebi.ac.uk/pdbsum/5a1k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5a1k ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chumnarnsilpa, S]] | + | [[Category: Chumnarnsilpa S]] |
| - | [[Category: Grimes, J M]] | + | [[Category: Grimes JM]] |
| - | [[Category: Leyrat, C]] | + | [[Category: Leyrat C]] |
| - | [[Category: Robinson, R C]] | + | [[Category: Robinson RC]] |
| - | [[Category: Actin]]
| + | |
| - | [[Category: Actin-binding protein]]
| + | |
| 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]
Publication Abstract from PubMed
Adseverin is a member of the calcium-regulated gelsolin superfamily of actin-binding proteins. Here we report the crystal structure of the calcium-free N-terminal half of adseverin (iA1-A3) and the Ca(2+)-bound structure of A3, which reveal structural similarities and differences with gelsolin. Solution small-angle X-ray scattering combined with ensemble optimization revealed a dynamic Ca(2+)-dependent equilibrium between inactive, intermediate and active conformations. Increasing calcium concentrations progressively shift this equilibrium from a main population of inactive conformation to the active form. Molecular dynamics simulations of iA1-A3 provided insights into Ca(2+)-induced destabilization, implicating a critical role for the A2 type II calcium-binding site and the A2A3 linker in the activation process. Finally, mutations that disrupt the A1/A3 interface increase Ca(2+)-independent F-actin severing by A1-A3, albeit at a lower efficiency than observed for gelsolin domains G1-G3. Together, these data address the calcium dependency of A1-A3 activity in relation to the calcium-independent activity of G1-G3.
Calcium-controlled conformational choreography in the N-terminal half of adseverin.,Chumnarnsilpa S, Robinson RC, Grimes JM, Leyrat C Nat Commun. 2015 Sep 14;6:8254. doi: 10.1038/ncomms9254. PMID:26365202[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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, 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
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