8w4b

The sigma-1 receptor from Xenopus laevis in complex with progesterone by co-crystallization

spinqualitylabelsall models 8w4b, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8w4b is a 1 chain structure with sequence from Xenopus laevis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.152Å Ligands: STR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SGMR1_XENLA May function in lipid transport from the endoplasmic reticulum and be involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. May regulate calcium efflux at the endoplasmic reticulum (By similarity). Publication Abstract from PubMed The sigma-1 receptor (sigma1R) is a non-opioid membrane receptor, which responds to a diverse array of synthetic ligands to exert various pharmacological effects. Meanwhile, candidates for endogenous ligands of sigma1R have also been identified. However, how endogenous ligands bind to sigma1R remains unknown. Here, we present crystal structures of sigma1R from Xenopus laevis (xlsigma1R) bound to two endogenous neurosteroid ligands, progesterone (a putative antagonist) and dehydroepiandrosterone sulfate (DHEAS) (a putative agonist), at 2.15-3.09 A resolutions. Both neurosteroids bind to a similar location in xlsigma1R mainly through hydrophobic interactions, but surprisingly, with opposite binding orientations. DHEAS also forms hydrogen bonds with xlsigma1R, whereas progesterone interacts indirectly with the receptor through water molecules near the binding site. Binding analyses are consistent with the xlsigma1R-neurosteroid complex structures. Furthermore, molecular dynamics simulations and structural data reveal a potential water entry pathway. Our results provide insight into binding of two endogenous neurosteroid ligands to sigma1R. Insight into binding of endogenous neurosteroid ligands to the sigma-1 receptor.,Fu C, Xiao Y, Zhou X, Sun Z Nat Commun. 2024 Jul 4;15(1):5619. doi: 10.1038/s41467-024-49894-7. PMID:38965213 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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