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| | <StructureSection load='5u85' size='340' side='right'caption='[[5u85]], [[Resolution|resolution]] 1.65Å' scene=''> | | <StructureSection load='5u85' size='340' side='right'caption='[[5u85]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5u85]] 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=5U85 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U85 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5u85]] 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=5U85 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U85 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Psap, Sgp1 ([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]] 1.65Å</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=5u85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u85 OCA], [http://pdbe.org/5u85 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u85 RCSB], [http://www.ebi.ac.uk/pdbsum/5u85 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u85 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=5u85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u85 OCA], [https://pdbe.org/5u85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u85 RCSB], [https://www.ebi.ac.uk/pdbsum/5u85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u85 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SAP_MOUSE SAP_MOUSE]] Prosaposin: Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling.<ref>PMID:23690594</ref> Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.[UniProtKB:P07602] Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.[UniProtKB:P07602] Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12).[UniProtKB:P07602] Saposins are specific low-molecular mass non-enzymic proteins, they participate in the lysosomal degradation of sphingolipids, which takes place by the sequential action of specific hydrolases.[UniProtKB:P07602] | + | [https://www.uniprot.org/uniprot/SAP_MOUSE SAP_MOUSE] Prosaposin: Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling.<ref>PMID:23690594</ref> Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.[UniProtKB:P07602] Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.[UniProtKB:P07602] Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12).[UniProtKB:P07602] Saposins are specific low-molecular mass non-enzymic proteins, they participate in the lysosomal degradation of sphingolipids, which takes place by the sequential action of specific hydrolases.[UniProtKB:P07602] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Gebai, A]] | + | [[Category: Gebai A]] |
| - | [[Category: Gorelik, A]] | + | [[Category: Gorelik A]] |
| - | [[Category: Illes, K]] | + | [[Category: Illes K]] |
| - | [[Category: Nagar, B]] | + | [[Category: Nagar B]] |
| - | [[Category: Lipid binding protein]]
| + | |
| - | [[Category: Saposin]]
| + | |
| Structural highlights
Function
SAP_MOUSE Prosaposin: Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling.[1] Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.[UniProtKB:P07602] Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.[UniProtKB:P07602] Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12).[UniProtKB:P07602] Saposins are specific low-molecular mass non-enzymic proteins, they participate in the lysosomal degradation of sphingolipids, which takes place by the sequential action of specific hydrolases.[UniProtKB:P07602]
Publication Abstract from PubMed
Saposins are accessory proteins that aid in the degradation of sphingolipids by hydrolytic enzymes. Their structure usually comprises four alpha-helices arranged in various conformations including an open, V-shaped form that is generally associated with the ability to interact with membranes and/or enzymes to accentuate activity. Saposin D is required by the lysosomal hydrolase, acid ceramidase, which breaks down ceramide into sphingosine and free fatty acid, to display optimal activity. The structure of saposin D was previously determined in an inactive conformation, revealing a monomeric, closed and compact form. Here, we present the crystal structure of the open, V-shaped form of saposin D. The overall shape is similar to the open conformation found in other saposins with slight differences in the angles between the alpha-helices. The structure forms a dimer that serves to stabilize the hydrophobic surface exposed in the open form, which results in an internal, hydrophobic cavity that could be used to carry extracted membrane lipids.
Crystal structure of saposin D in an open conformation.,Gebai A, Gorelik A, Nagar B J Struct Biol. 2018 Jul 17. pii: S1047-8477(18)30169-2. doi:, 10.1016/j.jsb.2018.07.011. PMID:30026085[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Meyer RC, Giddens MM, Schaefer SA, Hall RA. GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin. Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9529-34. doi:, 10.1073/pnas.1219004110. Epub 2013 May 20. PMID:23690594 doi:http://dx.doi.org/10.1073/pnas.1219004110
- ↑ Gebai A, Gorelik A, Nagar B. Crystal structure of saposin D in an open conformation. J Struct Biol. 2018 Jul 17. pii: S1047-8477(18)30169-2. doi:, 10.1016/j.jsb.2018.07.011. PMID:30026085 doi:http://dx.doi.org/10.1016/j.jsb.2018.07.011
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