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4a5k

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Revision as of 20:40, 5 August 2016

Structural analyses of Slm1-PH domain demonstrate ligand binding in the non-canonical site

Structural highlights

4a5k is a 4 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4a6f, 4a6h, 4a6k
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4]

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Audhya A, Loewith R, Parsons AB, Gao L, Tabuchi M, Zhou H, Boone C, Hall MN, Emr SD. Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton. EMBO J. 2004 Oct 1;23(19):3747-57. Epub 2004 Sep 16. PMID:15372071 doi:10.1038/sj.emboj.7600384
↑ Fadri M, Daquinag A, Wang S, Xue T, Kunz J. The pleckstrin homology domain proteins Slm1 and Slm2 are required for actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-bisphosphate and TORC2. Mol Biol Cell. 2005 Apr;16(4):1883-900. Epub 2005 Feb 2. PMID:15689497 doi:E04-07-0564
↑ Mulet JM, Martin DE, Loewith R, Hall MN. Mutual antagonism of target of rapamycin and calcineurin signaling. J Biol Chem. 2006 Nov 3;281(44):33000-7. Epub 2006 Sep 7. PMID:16959779 doi:M604244200
↑ Bultynck G, Heath VL, Majeed AP, Galan JM, Haguenauer-Tsapis R, Cyert MS. Slm1 and slm2 are novel substrates of the calcineurin phosphatase required for heat stress-induced endocytosis of the yeast uracil permease. Mol Cell Biol. 2006 Jun;26(12):4729-45. PMID:16738335 doi:10.1128/MCB.01973-05
↑ Anand K, Maeda K, Gavin AC. Structural Analyses of the Slm1-PH Domain Demonstrate Ligand Binding in the Non-Canonical Site. PLoS One. 2012;7(5):e36526. Epub 2012 May 4. PMID:22574179 doi:10.1371/journal.pone.0036526

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4a5k"

@@ Line 1: / Line 1: @@
 ==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]] 1.76&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4a5k]] is a 4 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A5K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4a5k]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A5K FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4a6f|4a6f]], [[4a6h|4a6h]], [[4a6k|4a6k]]</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=4a5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a5k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a5k RCSB], [http://www.ebi.ac.uk/pdbsum/4a5k PDBsum]</span></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=4a5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a5k OCA], [http://pdbe.org/4a5k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4a5k RCSB], [http://www.ebi.ac.uk/pdbsum/4a5k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4a5k ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, 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: Saccharomyces cerevisiae]]
+[[Category: Atcc 18824]]
 [[Category: Anand, K]]
 [[Category: Gavin, A C]]

4a5k

From Proteopedia

Revision as of 20:40, 5 August 2016

Structural analyses of Slm1-PH domain demonstrate ligand binding in the non-canonical site

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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