8GOC

Structure of beta-arrestin2 in complex with a phosphopeptide corresponding to the human Vasopressin V2 receptor, V2R

Summary for 8GOC

• Entry DOI: 10.2210/pdb8goc/pdb
• EMDB information: 34175
• Descriptor: Beta-arrestin-2, 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: 12
• Total formula weight: 299867.90

Authors

Maharana, J.,Sarma, P.,Yadav, M.K.,Banerjee, R.,Shukla, A.K. (deposition date: 2022-08-24, release date: 2023-05-17, Last modification date: 2024-07-17)

Primary citation

Maharana, J.,Sarma, P.,Yadav, M.K.,Saha, S.,Singh, V.,Saha, S.,Chami, M.,Banerjee, R.,Shukla, A.K.
Structural snapshots uncover a key phosphorylation motif in GPCRs driving beta-arrestin activation.
Mol.Cell, 83:2091-2107.e7, 2023

PubMed Abstract: Agonist-induced GPCR phosphorylation is a key determinant for the binding and activation of β-arrestins (βarrs). However, it is not entirely clear how different GPCRs harboring divergent phosphorylation patterns impart converging active conformation on βarrs leading to broadly conserved functional responses such as desensitization, endocytosis, and signaling. Here, we present multiple cryo-EM structures of activated βarrs in complex with distinct phosphorylation patterns derived from the carboxyl terminus of different GPCRs. These structures help identify a P-X-P-P type phosphorylation motif in GPCRs that interacts with a spatially organized K-K-R-R-K-K sequence in the N-domain of βarrs. Sequence analysis of the human GPCRome reveals the presence of this phosphorylation pattern in a large number of receptors, and its contribution in βarr activation is demonstrated by targeted mutagenesis experiments combined with an intrabody-based conformational sensor. Taken together, our findings provide important structural insights into the ability of distinct GPCRs to activate βarrs through a significantly conserved mechanism.

PubMed: 37209686
DOI: 10.1016/j.molcel.2023.04.025

Experimental method

ELECTRON MICROSCOPY (4.18 Å)