8ZJG

Cryo-EM structure of human CMKLR1-Gi complex bound to chemerin

Summary for 8ZJG

• Entry DOI: 10.2210/pdb8zjg/pdb
• EMDB information: 60144
• Descriptor: Chemerin-like receptor 1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(i) subunit alpha-1, ... (8 entities in total)
• Functional Keywords: chemerin receptor, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 171582.69

Authors

Liu, A.J.,Liu, Y.Z.,Ye, R.D. (deposition date: 2024-05-14, release date: 2025-01-22, Last modification date: 2025-07-02)

Primary citation

Liu, A.,Liu, Y.,Wang, J.,Ye, R.D.
Structural basis for full-length chemerin recognition and signaling through chemerin receptor 1.
Commun Biol, 7:1598-1598, 2024

PubMed Abstract: Chemerin, a chemotactic adipokine, plays essential roles in adipogenesis and inflammation. Serum chemerin concentration is closely associated with obesity and metabolism disorders. The mature form of chemerin (residues 21-157) acts primarily through chemerin receptor 1 (CMKLR1) for transmembrane signaling. As a result, CMKLR1 serves as a promising target for therapeutic intervention of immunometabolic diseases such as diabetes and multiple sclerosis. Here, we present a high-resolution cryo-EM structure of CMKLR1-Gi signaling complex bound to biologically active full-length chemerin. The mature chemerin shows binding features distinct from its C-terminal nonapeptide including interaction with both the extracellular loops (ECLs) and the N-terminus of CMKLR1. Combining results from functional assays, our studies demonstrate that chemerin interacts with CMKLR1 in a "two-site" mode similar to chemokine-chemokine receptor interactions, but acting as a "reverse chemokine" by inserting its C-terminus instead of the N-terminus as in the case of chemokines into the transmembrane binding pocket of CMKLR1. These structural insights are expected to help develop synthetic analogs with therapeutic potential.

PubMed: 39616240
DOI: 10.1038/s42003-024-07228-9

Experimental method

ELECTRON MICROSCOPY (3.18 Å)