4a5k
From Proteopedia
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| - | [[Image:4a5k.jpg|left|200px]] | ||
| - | + | ==Structural analyses of Slm1-PH domain demonstrate ligand binding in the non-canonical site== | |
| - | + | <StructureSection load='4a5k' size='340' side='right'caption='[[4a5k]], [[Resolution|resolution]] 1.76Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[4a5k]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A5K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A5K FirstGlance]. <br> | |
| - | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.76Å</td></tr> | |
| - | -- | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4a5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a5k OCA], [https://pdbe.org/4a5k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a5k RCSB], [https://www.ebi.ac.uk/pdbsum/4a5k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a5k ProSAT]</span></td></tr> | |
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SLM1_YEAST SLM1_YEAST] Together with SLM2, effector of the TORC2- and calcineurin-signaling pathways. Phosphorylated and activated by TORC2 under favorable growth conditions. Mediates actin polarization via inhibition of calcineurin-dependent transcription. Upon nutrient limitation or environmental stress, gets dephosphorylated by calcineurin. Dephosphorylation inhibits its interaction with TORC2, thereby antagonizing TORC2 signaling and mediating calcineurin-dependent actin depolarization. Also functions in heat-induced, calcineurin-mediated uracil permease (FUR4) endocytosis.<ref>PMID:15372071</ref> <ref>PMID:15689497</ref> <ref>PMID:16959779</ref> <ref>PMID:16738335</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | BACKGROUND: Pleckstrin homology (PH) domains are common membrane-targeting modules and their best characterized ligands are a set of important signaling lipids that include phosphatidylinositol phosphates (PtdInsPs). PH domains recognize PtdInsPs through two distinct mechanisms that use different binding pockets on opposite sides of the beta-strands 1 and 2: i) a canonical binding site delimited by the beta1-beta2 and beta3-beta4loops and ii) a non-canonical binding site bordered by the beta1-beta2 and beta5-beta6loops. The PH domain-containing protein Slm1 from budding yeast Saccharomyces cerevisiae is required for actin cytoskeleton polarization and cell growth. We recently reported that this PH domain binds PtdInsPs and phosphorylated sphingolipids in a cooperative manner. PRINCIPAL FINDINGS: To study the structural basis for the Slm1-PH domain (Slm1-PH) specificity, we co-crystallized this domain with different soluble compounds that have structures analogous to anionic lipid head groups of reported Slm1 ligands: inositol 4-phosphate, which mimics phosphatidylinositol-4-phosphate (PtdIns(4)P), and phosphoserine as a surrogate for dihydrosphingosine 1-phosphate (DHS1-P). We found electron densities for the ligands within the so-called non-canonical binding site. An additional positively charged surface that contacts a phosphate group was identified next to the canonical binding site. CONCLUSIONS: Our results suggest that Slm1-PH utilizes a non-canonical binding site to bind PtdInsPs, similar to that described for the PH domains of beta-spectrin, Tiam1 and ArhGAP9. Additionally, Slm1-PH may have retained an active canonical site. We propose that the presence of both a canonical and a non-canonical binding pocket in Slm1-PH may account for the cooperative binding to PtdInsPs and DHS-1P. | ||
| - | + | Structural Analyses of the Slm1-PH Domain Demonstrate Ligand Binding in the Non-Canonical Site.,Anand K, Maeda K, Gavin AC PLoS One. 2012;7(5):e36526. Epub 2012 May 4. PMID:22574179<ref>PMID:22574179</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 4a5k" style="background-color:#fffaf0;"></div> | |
| - | + | == References == | |
| - | + | <references/> | |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
| - | == | + | [[Category: Large Structures]] |
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[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
| - | [[Category: Anand | + | [[Category: Anand K]] |
| - | [[Category: Gavin | + | [[Category: Gavin AC]] |
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Current revision
Structural analyses of Slm1-PH domain demonstrate ligand binding in the non-canonical site
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