Fig. 8: Intrabody30 (Ib30) stabilizes the active conformation of βarr1.

a Structural snapshots of βarr1 crystal structures in complex with V₂Rpp^WT (PDB: 4JQI) and V₂Rpp^T360-1 (PDB: 7DFA). The superimposed structures display repositioning of the V₂Rpp^T360-1 N-terminal segment harboring Thr³⁶⁰ residue (cyan) relative to the V₂R^WT (green). Also, changes in ionic interactions of Thr³⁶⁰ with neighboring residues are shown. For the V₂R^WT bound βarr1, Thr³⁶⁰ engages with Lys²⁹⁴, Lys¹¹, and Arg²⁵. In the V₂R^T360-1 bound state, the Thr³⁶⁰ is non-phosphorylated, and the side-chain of Thr³⁵⁹ is repositioned to interact with Lys¹¹. b−d MD simulation of βarr1 in complex with either V₂Rpp^WT or V₂Rpp^T360A based on the crystal structure of V₂Rpp-βarr1 (PDB: 4JQI) reveals enrichment of inactive-like conformations of βarr1 in V₂Rpp^T360A-bound conformation. However, the binding of Fab30 to V₂Rpp^T360A-βarr1 complex robustly enriches the active-like conformational population of βarr1 as assessed by inter-domain rotation. The blue line in 8b represents the rolling averages, while the grey line represents the original values for interdomain rotation per frame. Source data are provided as a Source Data file.