8JAF

Structure of Muscarinic receptor (M2R) in complex with beta-arrestin1 (Local Refine, non-cross linked)

Summary for 8JAF

• Entry DOI: 10.2210/pdb8jaf/pdb
• EMDB information: 36126
• Descriptor: Beta-arrestin-1, Fab30 heavy chain, Fab30 light chain, ... (4 entities in total)
• Functional Keywords: gpcr, arrestin, signaling protein, signaling protein-immune system complex, signaling protein/immune system
• Biological source: Bos taurus (cattle); More
• Total number of polymer chains: 4
• Total formula weight: 65592.97

Authors

Maharana, J.,Sano, F.K.,Shihoya, W.,Banerjee, R.,Nureki, O.,Shukla, A.K. (deposition date: 2023-05-05, release date: 2023-12-27, Last modification date: 2024-10-23)

Primary citation

Maharana, J.,Sano, F.K.,Sarma, P.,Yadav, M.K.,Duan, L.,Stepniewski, T.M.,Chaturvedi, M.,Ranjan, A.,Singh, V.,Saha, S.,Mahajan, G.,Chami, M.,Shihoya, W.,Selent, J.,Chung, K.Y.,Banerjee, R.,Nureki, O.,Shukla, A.K.
Molecular insights into atypical modes of beta-arrestin interaction with seven transmembrane receptors.
Science, 383:101-108, 2024

PubMed Abstract: β-arrestins (βarrs) 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 βarrs either in the basal state, activated by the muscarinic receptor subtype 2 (M2R) through its third intracellular loop, or activated by the βarr-biased decoy D6 receptor (D6R). Combined with biochemical, cellular, and biophysical experiments, these structural snapshots allow the visualization of atypical engagement of βarrs with 7TMRs and also reveal a structural transition in the carboxyl terminus of βarr2 from a β strand to an α helix upon activation by D6R. Our study provides previously unanticipated molecular insights into the structural and functional diversity encoded in 7TMR-βarr complexes with direct implications for exploring novel therapeutic avenues.

PubMed: 38175886
DOI: 10.1126/science.adj3347

Experimental method

ELECTRON MICROSCOPY (3.1 Å)