Binding of inositol phosphates to arrestin

Palczewski, Krzysztof; Pulvermüller, Alexander; Buczyłko, Janina; Gutmann, Caroline; Hofmann, Klaus Peter

doi:10.1016/0014-5793(91)81416-6

Cited by 73 publications

(73 citation statements)

References 23 publications

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“…When the deutero-acetylation experiments were repeated in the presence of heparin, small decreases (<lo%) in acetylation were observed at 6 lysines with the greatest protection of highly polycationic peptide TV232-242 and peptide TV292-302 (data not shown), regions that were weakly protected during interaction with P-Rho*. These data are consistent with an overlap of binding regions for heparin and P-Rho* and for the reported competition between P-Rho* and heparin for the binding to arrestin (Palczewski et al, 1991b.…”

Section: Arrestin/p-rho* Interactionssupporting

confidence: 76%

Topographic study of arrestin using differential chemical modifications and hydrogen/deuterium exchange

Ohguro¹,

Palczewski²,

Walsh³

et al. 1994

Protein Science

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Arrestin is involved in the quenching of phototransduction by binding to photoactivated and phosphorylated rhodopsin (P-Rho*). To study its conformational changes and regions interacting with P-Rho*, arrestin was subjected to (1) differential acetylation at lysine residues in the presence and absence of P-Rho*, and (2) amide hydrogen/ deuterium exchange. Labeled protein was proteolysed and analyzed by mass spectrometry. Three Lys residues, 28, 176, and 21 I, were protected from acetylation in native arrestin, although they were not located in regions exhibiting slow amide hydrogen exchange rates. The presence of P-Rho* protected lysine 201 from acetylation and partially protected 14 other lysyl residues, including (2, 5 ) , (163, 166, 167), (232, 235, 236, 238), (267, 276), (298, 300), and 367, where parentheses indicate lysine residues found within the same peptide. In contrast, in the C-terminal region of arrestin, lysyl residues (386, 392, 395) were more exposed upon binding to P-Rho*. These data allowed us to identify functional regions in the arrestin molecule.

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Section: Arrestin/p-rho* Interactionssupporting

confidence: 76%

Topographic study of arrestin using differential chemical modifications and hydrogen/deuterium exchange

Ohguro¹,

Palczewski²,

Walsh³

et al. 1994

Protein Science

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“…These two interactions activate arrestin, allowing its transition into a high affinity receptor-binding state (2). Several lines of evidence suggest that a major conformational rearrangement of the arrestin molecule is a part of this transition (2)(3)(4)(5). First, arrestin binding to the receptor has a very high Arrhenius activation energy (3).…”

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confidence: 99%

Transition of Arrestin into the Active Receptor-binding State Requires an Extended Interdomain Hinge

Vishnivetskiy

Hirsch

Velez

et al. 2002

Journal of Biological Chemistry

111

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Arrestins selectively bind to the phosphorylated activated form of G protein-coupled receptors, thereby blocking further G protein activation. Structurally, arrestins consist of two domains topologically connected by a 12-residue long loop, which we term the "hinge" region. Both domains contain receptor-binding elements. The relative size and shape of arrestin and rhodopsin suggest that dramatic changes in arrestin conformation are required to bring all of its receptorbinding elements in contact with the cytoplasmic surface of the receptor. Here we use the visual arrestin/ rhodopsin system to test the hypothesis that the transition of arrestin into its active receptor-binding state involves a movement of the two domains relative to each other that might be limited by the length of the hinge. We have introduced three insertions and 24 deletions in the hinge region and measured the binding of all of these mutants to light-activated phosphorylated (P-Rh*), dark phosphorylated (P-Rh), dark unphosphorylated (Rh), and light-activated unphosphorylated rhodopsin (Rh*). The addition of 1-3 extra residues to the hinge has no effect on arrestin function. In contrast, sequential elimination of 1-8 residues results in a progressive decrease in P-Rh* binding without changing arrestin selectivity for P-Rh*. These results suggest that there is a minimum length of the hinge region necessary for high affinity binding, consistent with the idea that the two domains move relative to each other in the process of arrestin transition into its active receptor-binding state. The same length of the hinge is also necessary for the binding of "constitutively active" arrestin mutants to P-Rh*, dark P-Rh, and Rh*, suggesting that the active (receptorbound) arrestin conformation is essentially the same in both wild type and mutant forms.The signaling by a vast family of G protein-coupled receptors is quenched by the binding of arrestin proteins to activated receptors that have been phosphorylated by specific receptor kinases (1). Selective binding to an appropriate functional form of the receptor and timely dissociation are prerequisites for the proper function of arrestin in the cell (1, 2). Phosphorylation and activation recognition sites on arrestin bind simultaneously to the phosphorylated receptor C terminus and regions of receptor that change conformation upon activation, respectively (2). These two interactions activate arrestin, allowing its transition into a high affinity receptor-binding state (2). Several lines of evidence suggest that a major conformational rearrangement of the arrestin molecule is a part of this transition (2-5). First, arrestin binding to the receptor has a very high Arrhenius activation energy (3). Second, the susceptibility of arrestin to proteolysis upon its binding to phosphorylated and light-activated rhodopsin (P-Rh*) 1 changes dramatically (4). Third, an additional hydrophobic binding site, which is not involved in its interaction with light-activated (Rh*) or phosphorylated dark (P-Rh) rhodopsin participa...

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“…As mentioned before, the concave surface of the N-domain contains a cationic region that has been implicated in the recognition of the phosphorylated state of rhodopsin (21,31). Thus, in the case of the 162myc163-R*P interaction, the anti-Myc antibody may exert its inhibitory effect by shielding this cationic region.…”

Section: Fig 2 Binding Of Wild-type and Myc-tagged Arrestin Mutantsmentioning

confidence: 96%

“…6, lanes 11 and 12). Previous studies have shown that heparin and other negatively charged ligands such as light-activated phosphorylated rhodopsin or the synthetic 7PP are able to bind arrestin and induce a conformational change in the molecule (20,26,31,38). Although it has been determined that the conformational changes induced by these ligands may not be identical, an enhanced susceptibility to proteolysis of arrestin C terminus is a common effect (38).…”

Section: Fig 2 Binding Of Wild-type and Myc-tagged Arrestin Mutantsmentioning

confidence: 99%

“…6, lane 6). A cationic region beginning with residue Lys-163 in bovine visual arrestin has previously been hypothesized to represent a heparin recognition site based on its similarity to heparin binding motifs found in other proteins (31). DISCUSSION Several lines of study have focused on the identification of rhodopsin-binding sites on the arrestin molecule in order to understand the mechanism of its specific recognition of the light-activated and phosphorylated form of the receptor.…”

Section: Fig 2 Binding Of Wild-type and Myc-tagged Arrestin Mutantsmentioning

confidence: 99%

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Insertional Mutagenesis and Immunochemical Analysis of Visual Arrestin Interaction with Rhodopsin

Dinculescu

McDowell

Amici

et al. 2002

Journal of Biological Chemistry

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Visual arrestin inactivates the phototransduction cascade by specifically binding to light-activated phosphorylated rhodopsin. This study describes the combined use of insertional mutagenesis and immunochemical approaches to probe the structural determinants of arrestin function. Recombinant arrestins with insertions of a 10-amino acid c-Myc tag (EQKLISEEDL) were expressed in yeast and characterized. When the tag was placed on the C terminus after amino acid 399, between amino acids 99 and 100 or between residues 162 and 163, binding to rhodopsin was found to be very similar to that of wild-type arrestin. Two stable mutants with Myc insertions in the 68 -78 loop were also generated. Binding to rhodopsin was markedly decreased for one (72myc73) and completely abolished for the other (77myc78). Limited proteolysis assays using trypsin in the absence or presence of heparin were performed on all mutants and confirmed their overall conformational integrity. Rhodopsin binding to either 162myc163 or 72myc73 arrestins in solution was completely inhibited in the presence of less than a 2-fold molar excess of anti-Myc antibody relative to arrestin. In contrast, the antibody did not block the interaction of the 399myc or 99myc100 arrestins with rhodopsin. These results indicate that an interactive surface for rhodopsin is located on or near the concave region of the N-domain of arrestin.

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Binding of inositol phosphates to arrestin

Cited by 73 publications

References 23 publications

Topographic study of arrestin using differential chemical modifications and hydrogen/deuterium exchange

Topographic study of arrestin using differential chemical modifications and hydrogen/deuterium exchange

Transition of Arrestin into the Active Receptor-binding State Requires an Extended Interdomain Hinge

Insertional Mutagenesis and Immunochemical Analysis of Visual Arrestin Interaction with Rhodopsin

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