7XBX

Cryo-EM structure of the human chemokine receptor CX3CR1 in complex with CX3CL1 and Gi1

Summary for 7XBX

• Entry DOI: 10.2210/pdb7xbx/pdb
• EMDB information: 33108
• Descriptor: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (5 entities in total)
• Functional Keywords: g protein-coupled receptor, chemokine receptor, cx3cr1, cx3cl1, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 138885.65

Authors

Lu, M.,Zhao, W.,Han, S.,Zhu, Y.,Wu, B.,Zhao, Q. (deposition date: 2022-03-22, release date: 2022-07-13, Last modification date: 2024-10-30)

Primary citation

Lu, M.,Zhao, W.,Han, S.,Lin, X.,Xu, T.,Tan, Q.,Wang, M.,Yi, C.,Chu, X.,Yang, W.,Zhu, Y.,Wu, B.,Zhao, Q.
Activation of the human chemokine receptor CX3CR1 regulated by cholesterol.
Sci Adv, 8:eabn8048-eabn8048, 2022

PubMed Abstract: As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous ligand CX3CL1, which shows notable potential as a therapeutic target in atherosclerosis, cancer, and neuropathy. However, the drug development of CX3CR1 is hampered partially by the lack of structural information. Here, we present two cryo-electron microscopy structures of CX3CR1-G complexes in ligand-free and CX3CL1-bound states at 2.8- and 3.4-Å resolution, respectively. Together with functional data, the structures reveal the key factors that govern the recognition of CX3CL1 by both CX3CR1 and US28. A much smaller conformational change of helix VI upon activation than previously solved class A GPCR-G complex structures is observed in CX3CR1, which may correlate with three cholesterol molecules that play essential roles in conformation stabilization and signaling transduction. Thus, our data deepen the understanding of cholesterol modulation in GPCR (G protein-coupled receptor) signaling and provide insights into the diversity of G protein coupling.

PubMed: 35767622
DOI: 10.1126/sciadv.abn8048

Experimental method

ELECTRON MICROSCOPY (3.4 Å)