7p4t | pdb_00007p4t
Tetrameric structure of murine SapA
Structural highlights
FunctionSAP_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 PubMedSaposins are lipid transfer proteins required for the degradation of sphingolipids in the lysosome. These small proteins bind lipids by transitioning from a closed, monomeric state to an open conformation exposing a hydrophobic surface that binds and shields hydrophobic lipid tails from the aqueous environment. Saposins form a range of multimeric assemblies to encompass these bound lipids and present them to hydrolases in the lysosome. This lipid-binding property of human saposin A has been exploited to form lipoprotein nanodiscs suitable for structural studies of membrane proteins. Here we present the crystal structure of a unique tetrameric assembly of murine saposin A produced serendipitously, following modifications of published protocols for making lipoprotein nanodiscs. The structure of this new saposin oligomer highlights the diversity of tertiary arrangement that can be adopted by these important lipid transfer proteins. A Tetrameric Assembly of Saposin A: Increasing Structural Diversity in Lipid Transfer Proteins.,Shamin M, Spratley SJ, Graham SC, Deane JE Contact (Thousand Oaks). 2021 Jan;4:251525642110523. doi: , 10.1177/25152564211052382. Epub 2021 Nov 17. PMID:37143956[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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