Cooperative Control of Arrestin Activation By Membrane Lipids And Phosphorylation Barcodes
R) identifies phospho-motifs that potently activate Arr2. Moreover, the position of these motifs relative to the membrane determines Arr2 engagement, supporting a model of regional phosphorylation barcodes. Genome-wide motif analysis further links the phosphorylation barcode to predicted arrestin coupling strength and classification into Class A or Class B GPCRs. Finally, lipidated phosphopeptides inhibit GPCR-Arr2 interactions in live cells and enable structural characterization of Arr2-phosphopeptide complexes by cryo-electron microscopy, establishing a membrane-integrated framework for decoding arrestin response.
Authors
- Chun-Liang Chen (ORCID: https://orcid.org/0000-0003-4625-4340)
- Candice S. Klug (ORCID: https://orcid.org/0000-0003-4547-320X)
- Adriano Marchese
- Yu‐Chen Yen (ORCID: https://orcid.org/0000-0003-4308-9167)
- Qiuyan Chen (ORCID: https://orcid.org/0000-0002-6263-6843)
- Yasmin Aydin (ORCID: https://orcid.org/0000-0003-0024-7428)
- Ya Zhuo
Institutions
- Indiana University Health (US)
- Medical College of Wisconsin (US)
- University of South Florida (US)
- Moffitt Cancer Center (US)
- Indiana University Melvin and Bren Simon Comprehensive Cancer Center
- Indiana University – Purdue University Indianapolis (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-16
- DOI
- https://doi.org/10.64898/2026.04.13.718317
- Primary Topic
- Receptor Mechanisms and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ralph W. and Grace M. Showalter Research Trust Fund