Visual arrestin activity may be regulated by self-association

Visual arrestin is the protein responsible for rapid quenching of G-protein -coupled receptor signaling. Arrestin exists as a latent inhibitor which mu st be 'activated' upon contact with a phosphorylated receptor. X-ray crysta l structures of visual arrestin exhibit a tetrameric arrangement wherein an asymmetric dimer with an extensive interface between conformationally diff erent subunits is related to a second asymmetric dimer by a local two-fold rotation axis. To test the biological relevance of this molecular organizat ion in solution, we carried out a sedimentation, equilibrium analysis of ar restin at both crystallographic and physiological protein concentrations.. While the tetrameric form can exist at the high concentrations used in crys tallography experiments, we find that arrestin participates in a monomer/di mer equilibrium at concentrations more likely to be physiologically relevan t. Solution interaction analysis of a proteolytically modified, constitutiv ely active form of arrestin shows diminished dimerization. We propose that self-association of arrestin may provide a mechanism for regulation of arre stin activity by (i) ensuring an adequate supply for rapid quenching of the visual signal and. (ii) limiting the availability of active monomeric spec ies, thereby preventing inappropriate signal termination.