Beta-arrestin Mutants

Simple SummaryContent extracted from patent full text and abstract with AI.

This patent describes engineered mutant versions of beta-arrestin proteins, particularly arrestin-3, that contain specific amino acid substitutions. These mutant beta-arrestins show enhanced ability to interact with G protein-coupled receptors (GPCRs), and especially with the beta-2 adrenergic receptor (B2AR). The mutants exhibit increased sensitivity and efficacy in detecting activated GPCR states and can be used as sensitive biosensors or to stabilize GPCRs for drug discovery and structural studies. Tools such as vectors encoding these mutants and complexes with GPCRs are also provided.

Use CasesContent extracted from patent full text and abstract with AI.

• High-sensitivity biosensors for monitoring GPCR activation in cell-based assays.
• Cell-free or cell-based assays for drug screening targeting GPCRs, such as identifying new agonists or antagonists.
• Structural studies (e.g., X-ray crystallography or cryo-EM) of GPCR-arrestin complexes, especially in active conformations, to aid drug discovery and receptor mechanism analysis.
• Stabilization of difficult-to-study GPCRs to facilitate purification or structural elucidation.
• Research on GPCR signaling pathways in pharmacology, neuroscience, and immunology.

BenefitsContent extracted from patent full text and abstract with AI.

• Up to 30% increased efficacy in arrestin recruitment compared to wild-type, enabling more sensitive detection of GPCR activation.
• Ability to sense lower levels of activated GPCRs (increased sensitivity and potency).
• Improved stabilization of activated GPCR conformations, facilitating biophysical and structural studies.
• Increased signal-to-noise ratio in functional assays, particularly useful for GPCRs with low natural arrestin recruitment.
• Broad applicability to multiple species (human, mouse, rat, bovine) and different GPCRs within class A/adrenergic receptors.
• Potential improvement in in silico and experimental drug screening platforms for GPCR-targeting compounds.

Technical Classifications (CPCs)

Inventors & Applicants

Patent Abstract

The present invention relates to the field of arrestin mutants, especially mutants of beta-arrestin, a complex of the mutant beta-arrestin of the invention and a GPCR, and a vector encoding the mutant beta-arrestin of the invention.