title: Robust self-association is a common feature of mammalian visual arrestin-1.
abstract: Arrestin-1 binds light-activated phosphorhodopsin and ensures rapid signal termination. Its deficiency in humans and mice results in prolonged signaling and rod degeneration. However, most of the biochemical studies were performed on bovine arrestin-1, which was shown to self-associate forming dimers and tetramers, although only the monomer binds rhodopsin. It is unclear whether self-association is a property of arrestin-1 in all mammals or a specific feature of bovine protein. To address this issue, we compared self-association parameters of purified human and mouse arrestin-1 with those of its bovine counterpart using multiangle light scattering. We found that mouse and human arrestin-1 also robustly self-associate, existing in a monomer-dimer-tetramer equilibrium. Interestingly, the combination of dimerization and tetramerization constants in these three species is strikingly different. While tetramerization of bovine arrestin-1 is highly cooperative (K(D,dim)(4) > K(D,tet)), K(D,dim) ∼ K(D,tet) in the mouse form and K(D,dim) ≪ K(D,tet) in the human form. Importantly, in all three species at very high physiological concentrations of arrestin-1 in rod photoreceptors, most of it is predicted to exist in oligomeric form, with a relatively low concentration of the free monomer. Thus, it appears that maintenance of low levels of the active monomer is the biological role of arrestin-1 self-association.
authors.affiliation: University of California, Los Angeles, California 90095, United States.
authors.forename: Miyeon
authors.initials: M
authors.lastname: Kim
authors.forename: Susan M
authors.initials: SM
authors.lastname: Hanson
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Vishnivetskiy
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Song
authors.forename: Whitney M
authors.initials: WM
authors.lastname: Cleghorn
authors.forename: Wayne L
authors.initials: WL
authors.lastname: Hubbell
authors.forename: Vsevolod V
authors.initials: VV
authors.lastname: Gurevich
mesh_terms: D000818:Animals; D019390:Arrestins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D017354:Point Mutation; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011817:Rabbits; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism
chemical_list: D019390:Arrestins