Custom-designed proteins as novel therapeutic tools? The case of arrestins

摘要: Multiple genetic disorders can be associated with excessive signalling by mutant G-protein-coupled receptors (GPCRs) that are either constitutively active or have lost sites where phosphorylation GPCR kinases is necessary for desensitisation cognate arrestins. Phosphorylation-independent arrestin1 compensate defects in of the rhodopsin retinal rod cells, facilitating recovery, improving light responsiveness, and promoting photoreceptor survival. These proof-of-principle experiments show that, based on mechanistic understanding inner workings a protein, one modify its functional characteristics to generate custom-designed mutants improve balance congenital acquired disorders. Manipulations arrestin elements responsible scaffolding mitogen-activated protein kinase cascades binding other proteins involved life-or-death decisions cell likely yield affect survival proliferation desired direction. Although this approach still infancy, targeted redesign individual functions many offers promise completely new therapeutic toolbox huge potential.