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.
Hanson
Susan M
SM
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Vishnivetskiy
Sergey A
SA
Hubbell
Wayne L
WL
Gurevich
Vsevolod V
VV
D000818:Animals; D019393:Arrestin / Q000737:chemistry* / Q000378:metabolism; D019390:Arrestins / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D002850:Chromatography, Gel; D019281:Dimerization; D006801:Humans; D007834:Lasers; D008027:Light; D008970:Molecular Weight; D010833:Phytic Acid / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012542:Scattering, Radiation; D000071557:beta-Arrestins
D019393:Arrestin; D019390:Arrestins; D011994:Recombinant Proteins; C082333:arrestin3; D000071557:beta-Arrestins; D010833:Phytic Acid