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Mouse Spexin: (I) NMR Solution Structure, Docking Models for Receptor Binding, and Histological Expression at Tissue
Matthew K H Wong1, Mulan He1, Kong Hung Sze2
1School of Biological Sciences, The University of Hong Kong, Hong Kong, Hong Kong.
Frontiers in Endocrinology
|July 19, 2021
Summary
Spexin (SPX) structure and its interaction with GalR2/3 receptors were elucidated. Mouse SPX is a helical peptide, and its ubiquitous tissue distribution provides a basis for understanding its physiological roles.
Area of Science:
- Biochemistry and Molecular Biology
- Neuroendocrinology
- Structural Biology
Background:
- Spexin (SPX), a neuropeptide, is linked to metabolic and mood disorders.
- Previous research on SPX primarily used mouse models, but its structural details and receptor interactions were largely unknown.
- Understanding SPX structure and distribution is crucial for elucidating its physiological functions.
Purpose of the Study:
- To determine the solution structure of mouse spexin (SPX).
- To model the structural interactions between SPX and its potential receptors, GalR2 and GalR3.
- To investigate the tissue and cellular distribution of SPX in mice.
Main Methods:
- Circular Dichroism (CD) and Nuclear Magnetic Resonance (NMR) spectroscopies were used to determine the solution structure of mouse SPX.
- Homology modeling and Molecular Dynamics (MD) simulations were employed to predict SPX binding with GalR2 and GalR3 receptors.
- Reverse Transcription Polymerase Chain Reaction (RT-PCR) and immunohistochemical staining were used to analyze SPX expression and distribution in mouse tissues.
Main Results:
- Mouse SPX adopts a helical structure in solution, with a random coil N-terminus and an alpha-helix in the C-terminus.
- Structural models suggest SPX interacts with GalR2 and GalR3 via hydrogen bonding and hydrophobic interactions involving specific amino acid residues.
- SPX is ubiquitously expressed across 28 mouse tissues, with high levels in the brain, GI tract, liver, gonads, and adrenal glands; protein localization was confirmed in various organs and the hypothalamo-pituitary axis.
Conclusions:
- The study provides the first structural insights into mouse SPX and its potential interactions with GalR2/3 receptors.
- The ubiquitous expression pattern of SPX supports its broad physiological roles.
- These findings lay the groundwork for future research into the specific functions of SPX in various physiological processes.
