4a6f

Crystal structure of Slm1-PH domain in complex with Phosphoserine

spinqualitylabelsall models 4a6f, resolution 1.68Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4a6f is a 2 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.68Å Ligands: PO4, SEP 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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