6WWZ

Cryo-EM structure of the human chemokine receptor CCR6 in complex with CCL20 and a Go protein

Summary for 6WWZ

• Entry DOI: 10.2210/pdb6wwz/pdb
• EMDB information: 21950
• Descriptor: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, C-C motif chemokine 20, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• Functional Keywords: gpcr, chemokine, chemokine receptor, complex, membrane protein
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 6
• Total formula weight: 173507.66

Authors

Wasilko, D.J.,Johnson, Z.L.,Ammirati, M.,Han, S.,Wu, H. (deposition date: 2020-05-09, release date: 2020-06-24, Last modification date: 2024-10-30)

Primary citation

Wasilko, D.J.,Johnson, Z.L.,Ammirati, M.,Che, Y.,Griffor, M.C.,Han, S.,Wu, H.
Structural basis for chemokine receptor CCR6 activation by the endogenous protein ligand CCL20.
Nat Commun, 11:3031-3031, 2020

PubMed Abstract: Chemokines are important protein-signaling molecules that regulate various immune responses by activating chemokine receptors which belong to the G protein-coupled receptor (GPCR) superfamily. Despite the substantial progression of our structural understanding of GPCR activation by small molecule and peptide agonists, the molecular mechanism of GPCR activation by protein agonists remains unclear. Here, we present a 3.3-Å cryo-electron microscopy structure of the human chemokine receptor CCR6 bound to its endogenous ligand CCL20 and an engineered Go. CCL20 binds in a shallow extracellular pocket, making limited contact with the core 7-transmembrane (TM) bundle. The structure suggests that this mode of binding induces allosterically a rearrangement of a noncanonical toggle switch and the opening of the intracellular crevice for G protein coupling. Our results demonstrate that GPCR activation by a protein agonist does not always require substantial interactions between ligand and the 7TM core region.

PubMed: 32541785
DOI: 10.1038/s41467-020-16820-6

Experimental method

ELECTRON MICROSCOPY (3.34 Å)