8AS2

Structure of arrestin2 in complex with 4P CCR5 phosphopeptide and Fab30

Summary for 8AS2

• Entry DOI: 10.2210/pdb8as2/pdb
• Descriptor: Beta-arrestin-1, C-C chemokine receptor type 5, Fab30 heavy chain, ... (4 entities in total)
• Functional Keywords: arrestin, gpcr, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 92025.29

Authors

Isaikina, P.,Jakob, R.P.,Maier, T.,Grzesiek, S. (deposition date: 2022-08-18, release date: 2023-06-07, Last modification date: 2024-10-23)

Primary citation

Isaikina, P.,Petrovic, I.,Jakob, R.P.,Sarma, P.,Ranjan, A.,Baruah, M.,Panwalkar, V.,Maier, T.,Shukla, A.K.,Grzesiek, S.
A key GPCR phosphorylation motif discovered in arrestin2⋅CCR5 phosphopeptide complexes.
Mol.Cell, 83:2108-, 2023

PubMed Abstract: The two non-visual arrestins, arrestin2 and arrestin3, bind hundreds of GPCRs with different phosphorylation patterns, leading to distinct functional outcomes. Structural information on these interactions is available only for very few GPCRs. Here, we have characterized the interactions between the phosphorylated human CC chemokine receptor 5 (CCR5) and arrestin2. We identified several new CCR5 phosphorylation sites necessary for stable arrestin2 complex formation. Structures of arrestin2 in the apo form and complexes with CCR5 C-terminal phosphopeptides, together with NMR, biochemical, and functional assays, revealed three phosphoresidues in a pXpp motif that are essential for arrestin2 binding and activation. The identified motif appears responsible for robust arrestin2 recruitment in many other GPCRs. An analysis of receptor sequences and available structural and functional information provides hints on the molecular basis of arrestin2/arrestin3 isoform specificity. Our findings demonstrate how multi-site phosphorylation controls GPCR⋅arrestin interactions and provide a framework to probe the intricate details of arrestin signaling.

PubMed: 37244255
DOI: 10.1016/j.molcel.2023.05.002

Experimental method

X-RAY DIFFRACTION (3.2 Å)