Structural basis for chemokine receptor CCR6 activation by the endogenous protein ligand CCL20

David Jonathan Wasilko, Zachary Lee Johnson, Mark Ammirati, Ye Che, Matthew C. Griffor, Seungil Han and Huixian Wu ()
Additional contact information
David Jonathan Wasilko: Discovery Sciences, Medicine Design, Pfizer Worldwide Research and Development
Zachary Lee Johnson: Discovery Sciences, Medicine Design, Pfizer Worldwide Research and Development
Mark Ammirati: Discovery Sciences, Medicine Design, Pfizer Worldwide Research and Development
Ye Che: Discovery Sciences, Medicine Design, Pfizer Worldwide Research and Development
Matthew C. Griffor: Discovery Sciences, Medicine Design, Pfizer Worldwide Research and Development
Seungil Han: Discovery Sciences, Medicine Design, Pfizer Worldwide Research and Development
Huixian Wu: Discovery Sciences, Medicine Design, Pfizer Worldwide Research and Development

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-16820-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16820-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-16820-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().