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PDBsum entry 4zrg
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Signaling protein
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PDB id
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4zrg
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References listed in PDB file
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Key reference
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Title
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Structural evidence for the role of polar core residue arg175 in arrestin activation.
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Authors
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J.Granzin,
A.Stadler,
A.Cousin,
R.Schlesinger,
R.Batra-Safferling.
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Ref.
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Sci Rep, 2015,
5,
15808.
[DOI no: ]
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PubMed id
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Abstract
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Binding mechanism of arrestin requires photoactivation and phosphorylation of
the receptor protein rhodopsin, where the receptor bound phosphate groups cause
displacement of the long C-tail 'activating' arrestin. Mutation of arginine 175
to glutamic acid (R175E), a central residue in the polar core and previously
predicted as the 'phosphosensor' leads to a pre-active arrestin that is able to
terminate phototransduction by binding to non-phosphorylated, light-activated
rhodopsin. Here, we report the first crystal structure of a R175E mutant
arrestin at 2.7 Å resolution that reveals significant differences compared to
the basal state reported in full-length arrestin structures. These differences
comprise disruption of hydrogen bond network in the polar core, and
three-element interaction including disordering of several residues in the
receptor-binding finger loop and the C-terminus (residues 361-404).
Additionally, R175E structure shows a 7.5° rotation of the amino and
carboxy-terminal domains relative to each other. Consistent to the biochemical
data, our structure suggests an important role of R29 in the initial activation
step of C-tail release. Comparison of the crystal structures of basal arrestin
and R175E mutant provide insights into the mechanism of arrestin activation,
where binding of the receptor likely induces structural changes mimicked as in
R175E.
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