8GO8
Structure of beta-arrestin1 in complex with a phosphopeptide corresponding to the human C5a anaphylatoxin chemotactic receptor 1, C5aR1
Summary for 8GO8
Entry DOI | 10.2210/pdb8go8/pdb |
EMDB information | 34173 |
Descriptor | Beta-arrestin-1, C5a anaphylatoxin chemotactic receptor 1, Fab30 heavy chain, ... (4 entities in total) |
Functional Keywords | gpcr, arrestin, signaling protein, signaling protein-immune system complex, signaling protein/immune system |
Biological source | Rattus norvegicus (Norway rat) More |
Total number of polymer chains | 8 |
Total formula weight | 197468.53 |
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 Cited by 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: 37209686DOI: 10.1016/j.molcel.2023.04.025 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (3.41 Å) |
Structure validation
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