Work

Structural insights into the binding modes of Arrestin-3 finger loop to the neuropeptide Y1 and Y2 receptors

Year: 2025

Type: article

Abstract: The interaction of the finger loop sequence of arrestin-3 with the neuropeptide Y 1 and Y 2 G protein-coupled receptors was studied. In cell assays, the finger loop part of arrestin was shown to be essential for Y 2 R internalization, but had no relevance for the interaction with Y 1 R. Here, we combined experimental data from nanoBRET, EPR, and NMR spectroscopy studies using a small library of NMR- and EPR-labeled finger loop peptides. Computer models of arrestin interacting with both receptors were built using AlphaFold2 and filtered by experimental constraints. Overall, Y 1 and Y 2 receptors show different binding modalities with the interacting finger loop region. In the interaction with Y 1 receptor, the finger loop features a tail conformation critical for binding but also optional interactions. The Y 2 receptor showed fewer contacts with the finger loop and two different conformations were found, which allow for higher intrinsic flexibility of this arrestin-3 segment.

Source: Structure

DOI: 10.1016/j.str.2025.07.012