4omk

Crystal structure of SPF bound to squalene

spinqualitylabelsall models 4omk, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4omk is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.75Å Ligands: CL, IPA, SO4, SQL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function S14L2_HUMAN Carrier protein. Binds to some hydrophobic molecules and promotes their transfer between the different cellular sites. Binds with high affinity to alpha-tocopherol. Also binds with a weaker affinity to other tocopherols and to tocotrienols. May have a transcriptional activatory activity via its association with alpha-tocopherol. Probably recognizes and binds some squalene structure, suggesting that it may regulate cholesterol biosynthesis by increasing the transfer of squalene to a metabolic active pool in the cell. Publication Abstract from PubMed We present the crystal structures of the SEC14-like domain of supernatant protein factor (SPF) in complex with squalene and 2,3-oxidosqualene. The structures were resolved at 1.75A (complex with squalene) and 1.6A resolution (complex with 2,3-oxidosqualene), leading in both cases to clear images of the protein/substrate interactions. Ligand binding is facilitated by removal of the Golgi-dynamics (GOLD) C-terminal domain of SPF, which, as shown in previous structures of the apo-protein, blocked the opening of the binding pocket to the exterior. Both substrates bind into a large hydrophobic cavity, typical of such lipid-transporter family. Our structures report no specific recognition mode for the epoxide group. In fact, for both molecules, ligand affinity is dominated by hydrophobic interactions, and independent investigations by computational models or differential scanning micro-calorimetry reveal similar binding affinities for both ligands. Our findings elucidate the molecular bases of the role of SPF in sterol endo-synthesis, supporting the original hypothesis that SPF is a facilitator of substrate flow within the sterol synthetic pathway. Moreover, our results suggest that the GOLD domain acts as a regulator, as its conformational displacement must occur to favor ligand binding and release during the different synthetic steps. Structural insights on cholesterol endosynthesis: Binding of squalene and 2,3-oxidosqualene to supernatant protein factor.,Christen M, Marcaida MJ, Lamprakis C, Aeschimann W, Vaithilingam J, Schneider P, Hilbert M, Schneider G, Cascella M, Stocker A J Struct Biol. 2015 Jun;190(3):261-70. doi: 10.1016/j.jsb.2015.05.001. Epub 2015 , May 16. PMID:25987292 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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