PDBsum entry 4zrg

Signaling protein

PDB id: 4zrg

Contents

Protein chain

343 a.a.

Ligands

CO2 ×5

Waters ×54

PDB id:

4zrg

Name:

Signaling protein

Title:

Visual arrestin mutant - r175e

Structure:

S-arrestin. Chain: a. Synonym: 48 kda protein,retinal s-antigen,s-ag,rod photoreceptor arrestin. Engineered: yes. Mutation: yes. Other_details: n-terminal tag -7 to 0: wshpqfek c-terminal tag: hhhhhh pointmutation: r175e

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Gene: sag. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932

Resolution:

2.70Å R-factor: 0.196 R-free: 0.241

Authors:

J.Granzin,A.Stadler,A.Cousin,R.Schlesinger,R.Batra-Safferling

Key ref:

J.Granzin et al. (2015). Structural evidence for the role of polar core residue Arg175 in arrestin activation. Sci Rep, 5, 15808. PubMed id: 26510463 DOI: 10.1038/srep15808

Date:

12-May-15 Release date: 11-Nov-15

Protein chain

P08168  (ARRS_BOVIN) -  S-arrestin from Bos taurus

Seq: 404 a.a.

Struc: 343 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1038/srep15808

Sci Rep 5:15808 (2015)

PubMed id: 26510463

Structural evidence for the role of polar core residue Arg175 in arrestin activation.

J.Granzin, A.Stadler, A.Cousin, R.Schlesinger, R.Batra-Safferling.

ABSTRACT

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.