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| | ==Crystal structure of talin autoinhibition complex== | | ==Crystal structure of talin autoinhibition complex== |
| - | <StructureSection load='4f7g' size='340' side='right' caption='[[4f7g]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='4f7g' size='340' side='right'caption='[[4f7g]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4f7g]] is a 2 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=4F7G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F7G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4f7g]] is a 2 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=4F7G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F7G FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tln1, Tln ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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]] 2.05Å</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=4f7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f7g OCA], [http://pdbe.org/4f7g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f7g RCSB], [http://www.ebi.ac.uk/pdbsum/4f7g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f7g 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=4f7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f7g OCA], [https://pdbe.org/4f7g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f7g RCSB], [https://www.ebi.ac.uk/pdbsum/4f7g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f7g ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TLN1_MOUSE TLN1_MOUSE]] Probably involved in connections of major cytoskeletal structures to the plasma membrane. High molecular weight cytoskeletal protein concentrated at regions of cell-substratum contact and, in lymphocytes, at cell-cell contacts. | + | [https://www.uniprot.org/uniprot/TLN1_MOUSE TLN1_MOUSE] Probably involved in connections of major cytoskeletal structures to the plasma membrane. High molecular weight cytoskeletal protein concentrated at regions of cell-substratum contact and, in lymphocytes, at cell-cell contacts. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | The activation of heterodimeric (alpha/beta) integrin transmembrane receptors by cytosolic protein talin is crucial for regulating diverse cell-adhesion-dependent processes, including blood coagulation, tissue remodeling, and cancer metastasis. This process is triggered by the coincident binding of N-terminal FERM (four-point-one-protein/ezrin/radixin/moesin) domain of talin (talin-FERM) to the inner membrane surface and integrin beta cytoplasmic tail, but how these binding events are spatiotemporally regulated remains obscure. Here we report the crystal structure of a dormant talin, revealing how a C-terminal talin rod segment (talin-RS) self-masks a key integrin-binding site on talin-FERM via a large interface. Unexpectedly, the structure also reveals a distinct negatively charged surface on talin-RS that electrostatically hinders the talin-FERM binding to the membrane. Such a dual inhibitory topology for talin is consistent with the biochemical and functional data, but differs significantly from a previous model. We show that upon enrichment with phosphotidylinositol-4,5-bisphosphate (PIP2) - a known talin activator, membrane strongly attracts a positively charged surface on talin-FERM and simultaneously repels the negatively charged surface on talin-RS. Such an electrostatic "pull-push" process promotes the relief of the dual inhibition of talin-FERM, which differs from the classic "steric clash" model for conventional PIP2-induced FERM domain activation. These data therefore unravel a new type of membrane-dependent FERM domain regulation and illustrate how it mediates the talin on/off switches to regulate integrin transmembrane signaling and cell adhesion.Cell Research advance online publication 19 June 2012; doi:10.1038/cr.2012.97.
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| - | A novel membrane-dependent on/off switch mechanism of talin FERM domain at sites of cell adhesion.,Song X, Yang J, Hirbawi J, Ye S, Perera HD, Goksoy E, Dwivedi P, Plow EF, Zhang R, Qin J Cell Res. 2012 Jun 19. doi: 10.1038/cr.2012.97. PMID:22710802<ref>PMID:22710802</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 4f7g" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
| - | *[[Talin|Talin]] | + | *[[Talin 3D structures|Talin 3D structures]] |
| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Qin, J]] | + | [[Category: Mus musculus]] |
| - | [[Category: Song, X]] | + | [[Category: Qin J]] |
| - | [[Category: Ye, S]] | + | [[Category: Song X]] |
| - | [[Category: Zhang, R]] | + | [[Category: Ye S]] |
| - | [[Category: Alpha-helix bundle]]
| + | [[Category: Zhang R]] |
| - | [[Category: Cell adhesion]]
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| - | [[Category: Integrin activation]]
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