Opposing Effects of Inositol Hexakisphosphate on Rod Arrestin and Arrestin2 Self-Association

The robust cooperative formation of rod arrestin tetramers has been well-established, whereas the ability of other members of the arrestin family to self-associate remains controversial. Here, we used purified arrestins and multi-angle light scattering to quantitatively compare the propensity of the four mammalian arrestin subtypes to self-associate. Both non-visual and cone arrestins only form oligomers at very high non-physiological concentrations. However, inositol hexakisphosphate (IP6), a fairly abundant form of inositol in the cytoplasm, greatly facilitates self-association of arrestin2. Arrestin2 self-association equilibrium constants in the presence of 100 microM IP6 suggest that an appreciable proportion could exist in an oligomeric state but only in intracellular compartments where its concentration is 5-10-fold higher than average. In contrast to arrestin2, IP6 inhibits self-association of rod arrestin, indicating that the structure of these two tetramers in solution is likely different.