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Comment
. 2023 Jan;44(1):1-3.
doi: 10.1016/j.tips.2022.08.005. Epub 2022 Aug 31.

Structural snapshot of a β-arrestin-biased receptor

Parishmita Sarma  1 , Ramanuj Banerjee  1 , Arun K Shukla  2
Affiliations
Comment

Structural snapshot of a β-arrestin-biased receptor

Parishmita Sarma et al. Trends Pharmacol Sci. 2023 Jan.

Abstract

Atypical chemokine receptor subtype 3 (ACKR3), a chemokine receptor, couples selectively to β-arrestins (βarrs) but not to G proteins despite having seven transmembrane (7TM) helix architecture. Yen et al. present cryogenic-electron microscopy (cryo-EM) structures of agonist-bound ACKR3, elucidating a distinct chemokine-binding mechanism, and offering a structural template to probe the transducer-coupling bias at this receptor.

Keywords: ACKR3; ACRs; GPCRs; biased agonism; chemokines; intrinsic bias; β-arrestins.

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Conflict of interest statement

Declaration of interests The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Chemokine recognition and activation of atypical chemokine receptor subtype 3 (ACKR3).
(A) Overall structural snapshot of CXCL12–ACKR3 in the presence of two stabilizing antigen-binding fragments of antibodies (FABs) (CID25 and CID24). (B) Distinct binding pose of CXCL12 to ACKR3 compared with CXCL8 and viral macrophage inflammatory protein II (vMIP-II) on CXCR2 and CXCR4, respectively. (C) Transmembrane helix 4 (TM4) in ACKR3 is an extended conformation at the cytoplasmic end while it exhibits a kink in the CXCL8-bound CXCR2 structure. These structural snapshots are designed based on PDB ID 7SK3, 6LFO, and 4RWS for ACKR3, CXCR2, and CXCR4, respectively. Abbreviations: ACR, arrestin-coupled receptor; GPCR, G protein-coupled receptor.
See this image and copyright information in PMC

Comment on

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