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TitleActivation of the human chemokine receptor CX3CR1 regulated by cholesterol.
Journal, issue, pagesSci Adv, Vol. 8, Issue 26, Page eabn8048, Year 2022
Publish dateJun 29, 2022
AuthorsMinmin Lu / Wenli Zhao / Shuo Han / Xiaowen Lin / Tingyu Xu / Qiuxiang Tan / Mu Wang / Cuiying Yi / Xiaojing Chu / Weibo Yang / Ya Zhu / Beili Wu / Qiang Zhao /
PubMed AbstractAs 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 ...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.
External linksSci Adv / PubMed:35767622 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.4 Å
Structure data

33107

7xbw

EMDB-33107, PDB-7xbw:
Cryo-EM structure of the human chemokine receptor CX3CR1 in complex with Gi1
Method: EM (single particle) / Resolution: 2.8 Å

33108

7xbx

EMDB-33108, PDB-7xbx:
Cryo-EM structure of the human chemokine receptor CX3CR1 in complex with CX3CL1 and Gi1
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-CLR:
CHOLESTEROL

Source
  • homo sapiens (human)
KeywordsSIGNALING PROTEIN / G protein-coupled receptor / chemokine receptor / CX3CR1 / CX3CL1

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