8W4D

Crystal structure of the sigma-1 receptor from Xenopus laevis in the absence of known ligands


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.17 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.214 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


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Literature

Insight into binding of endogenous neurosteroid ligands to the sigma-1 receptor.

Fu, C.Xiao, Y.Zhou, X.Sun, Z.

(2024) Nat Commun 15: 5619-5619

  • DOI: https://doi.org/10.1038/s41467-024-49894-7
  • Primary Citation of Related Structures:  
    8W4B, 8W4C, 8W4D, 8W4E, 8WUE, 8WWB, 8YBB

  • PubMed Abstract: 

    The sigma-1 receptor (σ1R) 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 σ1R have also been identified. However, how endogenous ligands bind to σ1R remains unknown. Here, we present crystal structures of σ1R from Xenopus laevis (xlσ1R) bound to two endogenous neurosteroid ligands, progesterone (a putative antagonist) and dehydroepiandrosterone sulfate (DHEAS) (a putative agonist), at 2.15-3.09  Å resolutions. Both neurosteroids bind to a similar location in xlσ1R mainly through hydrophobic interactions, but surprisingly, with opposite binding orientations. DHEAS also forms hydrogen bonds with xlσ1R, whereas progesterone interacts indirectly with the receptor through water molecules near the binding site. Binding analyses are consistent with the xlσ1R-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 σ1R.


  • Organizational Affiliation

    Department of Integrated Traditional Chinese and Western Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Sigma non-opioid intracellular receptor 1233Xenopus laevisMutation(s): 0 
Gene Names: sigmar1
Membrane Entity: Yes 
UniProt
Find proteins for Q6DCU6 (Xenopus laevis)
Explore Q6DCU6 
Go to UniProtKB:  Q6DCU6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6DCU6
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.17 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.214 
  • Space Group: I 4 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 160.49α = 90
b = 160.49β = 90
c = 160.49γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Aimlessdata scaling
XDSdata reduction
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Natural Science Foundation of China (NSFC)China31770783

Revision History  (Full details and data files)

  • Version 1.0: 2024-07-17
    Type: Initial release