| Structural highlights
Publication Abstract from PubMed
beta-arrestins (betaarrs) are multifunctional proteins involved in signaling and regulation of seven transmembrane receptors (7TMRs), and their interaction is driven primarily by agonist-induced receptor activation and phosphorylation. Here, we present seven cryo-electron microscopy structures of betaarrs either in the basal state, activated by the muscarinic receptor subtype 2 (M2R) through its third intracellular loop, or activated by the betaarr-biased decoy D6 receptor (D6R). Combined with biochemical, cellular, and biophysical experiments, these structural snapshots allow the visualization of atypical engagement of betaarrs with 7TMRs and also reveal a structural transition in the carboxyl terminus of betaarr2 from a beta strand to an alpha helix upon activation by D6R. Our study provides previously unanticipated molecular insights into the structural and functional diversity encoded in 7TMR-betaarr complexes with direct implications for exploring novel therapeutic avenues.
Molecular insights into atypical modes of beta-arrestin interaction with seven transmembrane receptors.,Maharana J, Sano FK, Sarma P, Yadav MK, Duan L, Stepniewski TM, Chaturvedi M, Ranjan A, Singh V, Saha S, Mahajan G, Chami M, Shihoya W, Selent J, Chung KY, Banerjee R, Nureki O, Shukla AK Science. 2024 Jan 5;383(6678):101-108. doi: 10.1126/science.adj3347. Epub 2024 , Jan 4. PMID:38175886[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Maharana J, Sano FK, Sarma P, Yadav MK, Duan L, Stepniewski TM, Chaturvedi M, Ranjan A, Singh V, Saha S, Mahajan G, Chami M, Shihoya W, Selent J, Chung KY, Banerjee R, Nureki O, Shukla AK. Molecular insights into atypical modes of β-arrestin interaction with seven transmembrane receptors. Science. 2024 Jan 5;383(6678):101-108. PMID:38175886 doi:10.1126/science.adj3347
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