科研之友
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摘要
beta-Arrestins (beta arrs) interact with G protein-coupled receptors (GPCRs) to desensitize G protein signaling, to initiate signaling on their own, and to mediate receptor endocytosis. Prior structural studies have revealed two unique conformations of GPCR-beta arr complexes: the "tail" conformation, with beta arr primarily coupled to the phosphorylated GPCR C-terminal tail, and the "core" conformation, where, in addition to the phosphorylated C-terminal tail, beta arr is further engaged with the receptor transmembrane core. However, the relationship of these distinct conformations to the various functions of beta arrs is unknown. Here, we created a mutant form of beta arr lacking the "finger-loop" region, which is unable to form the core conformation but retains the ability to form the tail conformation. We find that the tail conformation preserves the ability to mediate receptor internalization and beta arr signaling but not desensitization of G protein signaling. Thus, the two GPCR-beta arr conformations can carry out distinct functions.
