1zsh
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(New page: 200px<br /><applet load="1zsh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zsh, resolution 2.9Å" /> '''Crystal structure of ...)
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Revision as of 05:31, 21 November 2007
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Crystal structure of bovine arrestin-2 in complex with inositol hexakisphosphate (IP6)
Overview
Interactions between arrestins and phosphoinositides have been reported to, regulate multiple membrane-associated signaling and trafficking events, including clathrin-mediated endocytosis and light adaptation in, Drosophila. Arrestins have been proposed to have nuclear and cytosolic, functions as well, although the ligand dependence of these functions has, not been investigated. Here we characterize the structural, molecular, and, cellular interactions between arrestin-2 and inositol hexakisphosphate, (inositol 1,2,3,4,5,6-hexakisphosphate (IP(6))). The crystal structure of, the arrestin-2.IP(6) complex was solved to 2.9 A with crystal lattice, contacts suggesting two sites on a protein monomer mediating IP(6), binding. Mutagenesis coupled to isothermal titration calorimetry and, tritiated IP(6) binding assays confirmed two-site binding with a low, affinity IP(6)-binding site in the N-domain and a high affinity site in, the C-domain. Native gel electrophoresis, gel filtration, and analytical, ultracentrifugation demonstrated the ability of IP(6) to promote, arrestin-2 oligomerization via the two crystallographically defined, ligand-binding locations. In addition, analysis in mammalian cells, revealed that arrestin-2 not only undergoes homo-oligomerization, but it, can also hetero-oligomerize with arrestin-3 in a manner that depends on, IP(6)-binding sites. Mutation of either IP(6)-binding site in arrestin-2, disrupted oligomerization while interactions with known binding partners, including clathrin, AP-2, and ERK2 were maintained. Subcellular, localization studies showed that arrestin-2 oligomers are primarily, cytoplasmic, whereas arrestin-2 monomers displayed increased nuclear, localization. Thus, by promoting cytosolic oligomerization, IP(6) binding, is proposed to be a negative regulator of interactions of arrestin with, plasma membrane and nuclear signaling proteins.
About this Structure
1ZSH is a Single protein structure of sequence from Bos taurus with MG and IHP as ligands. Full crystallographic information is available from OCA.
Reference
Nonvisual arrestin oligomerization and cellular localization are regulated by inositol hexakisphosphate binding., Milano SK, Kim YM, Stefano FP, Benovic JL, Brenner C, J Biol Chem. 2006 Apr 7;281(14):9812-23. Epub 2006 Jan 26. PMID:16439357
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