Involvement of distinct arrestin-1 elements in binding to different functional forms of rhodopsin.

Zhuang T, Chen Q, Cho MK, Vishnivetskiy SA, Iverson TM, Gurevich VV, Sanders CR
Proc Natl Acad Sci U S A. 2013 110 (3): 942-7

PMID: 23277586 · PMCID: PMC3549108 · DOI:10.1073/pnas.1215176110

Solution NMR spectroscopy of labeled arrestin-1 was used to explore its interactions with dark-state phosphorylated rhodopsin (P-Rh), phosphorylated opsin (P-opsin), unphosphorylated light-activated rhodopsin (Rh*), and phosphorylated light-activated rhodopsin (P-Rh*). Distinct sets of arrestin-1 elements were seen to be engaged by Rh* and inactive P-Rh, which induced conformational changes that differed from those triggered by binding of P-Rh*. Although arrestin-1 affinity for Rh* was seen to be low (K(D) > 150 μM), its affinity for P-Rh (K(D) ~80 μM) was comparable to the concentration of active monomeric arrestin-1 in the outer segment, suggesting that P-Rh generated by high-gain phosphorylation is occupied by arrestin-1 under physiological conditions and will not signal upon photo-activation. Arrestin-1 was seen to bind P-Rh* and P-opsin with fairly high affinity (K(D) of~50 and 800 nM, respectively), implying that arrestin-1 dissociation is triggered only upon P-opsin regeneration with 11-cis-retinal, precluding noise generated by opsin activity. Based on their observed affinity for arrestin-1, P-opsin and inactive P-Rh very likely affect the physiological monomer-dimer-tetramer equilibrium of arrestin-1, and should therefore be taken into account when modeling photoreceptor function. The data also suggested that complex formation with either P-Rh* or P-opsin results in a global transition in the conformation of arrestin-1, possibly to a dynamic molten globule-like structure. We hypothesize that this transition contributes to the mechanism that triggers preferential interactions of several signaling proteins with receptor-activated arrestins.

MeSH Terms (16)

Arrestin Binding Sites Humans Kinetics Models, Molecular Multiprotein Complexes Mutagenesis, Insertional Nuclear Magnetic Resonance, Biomolecular Opsins Phosphorylation Photochemical Processes Protein Binding Protein Conformation Protein Interaction Domains and Motifs Recombinant Proteins Rhodopsin

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