PDBsum entry 1vqx

Signaling protein

PDB id: 1vqx

Contents

Protein chain

19 a.a.

PDB id:

1vqx

Name:

Signaling protein

Title:

Arrestin-bound nmr structures of the phosphorylated carboxy-terminal domain of rhodopsin, refined

Structure:

Rhodopsin. Chain: a. Fragment: c-terminal domain. Engineered: yes

Source:

Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence of the peptide is naturally found in bos taurus.

NMR struc:

15 models

Authors:

O.G.Kisselev,M.A.Downs,J.H.Mcdowell,P.A.Hargrave

Key ref:

O.G.Kisselev et al. (2004). Conformational changes in the phosphorylated C-terminal domain of rhodopsin during rhodopsin arrestin interactions. J Biol Chem, 279, 51203-51207. PubMed id: 15351781 DOI: 10.1074/jbc.M407341200

Date:

07-Jan-05 Release date: 18-Jan-05

Supersedes:

1tqk

Protein chain

P02699  (OPSD_BOVIN) -  Rhodopsin from Bos taurus

Seq: 348 a.a.

Struc: 19 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1074/jbc.M407341200

J Biol Chem 279:51203-51207 (2004)

PubMed id: 15351781

Conformational changes in the phosphorylated C-terminal domain of rhodopsin during rhodopsin arrestin interactions.

O.G.Kisselev, M.A.Downs, J.H.McDowell, P.A.Hargrave.

ABSTRACT

Phosphorylation of activated G-protein-coupled receptors and the subsequent binding of arrestin mark major molecular events of homologous desensitization. In the visual system, interactions between arrestin and the phosphorylated rhodopsin are pivotal for proper termination of visual signals. By using high resolution proton nuclear magnetic resonance spectroscopy of the phosphorylated C terminus of rhodopsin, represented by a synthetic 7-phosphopolypeptide, we show that the arrestin-bound conformation is a well ordered helix-loop structure connected to rhodopsin via a flexible linker. In a model of the rhodopsin-arrestin complex, the phosphates point in the direction of arrestin and form a continuous negatively charged surface, which is stabilized by a number of positively charged lysine and arginine residues of arrestin. Opposite to the mostly extended structure of the unphosphorylated C-terminal domain of rhodopsin, the arrestin-bound C-terminal helix is a compact domain that occupies a central position between the cytoplasmic loops and occludes the key binding sites of transducin. In conjunction with other binding sites, the helix-loop structure provides a mechanism of shielding phosphates in the center of the rhodopsin-arrestin complex and appears critical in guiding arrestin for high affinity binding with rhodopsin.

Selected figure(s)

Figure 4.
FIG. 4. a, ribbon model of bovine rhodopsin in blue with phosphorylated C-terminal domain shown in yellow in arrestin-bound conformation. Side chains of phosphorylated serines and threonines are shown as ball-and-stick models. Semi-transparent solvent-accessible surface of the phosphate groups is shown in red. Position of the transmembrane helices of rhodopsin is labeled. b, van der Waals surface of rhodopsin (cytoplasmic side) as seen by arrestin with the electrostatic potential mapped. White, neutral; red, negatively charged; blue, positively charged. The phospho-groups on Ser-334, Thr-335, Thr-336, Ser-338, Thr-340, Thr-342, and Ser-343 together with carboxyl groups of Glu-332 and Glu-341 form a continuous negatively charged surface. C2 and C3 show position of cytoplasmic loops two and three.

Figure 5.
FIG. 5. A model of rhodopsin-arrestin complex. Docking of arrestin to rhodopsin with phosphorylated Rh-(330-348) region in arrestin-bound state was manual, assuming interaction of the phosphate groups with region 166-179 of arrestin, a site of rhodopsin interactions with the most concentration of arginine and lysine residues. -Strands containing the region 166-179 and segments determining receptor specificity are in purple. Inset highlights the interaction site. Phosphate groups of rhodopsin are shown in red and labeled according to the phosphorylated residue number. Lysine and arginine side chains positioned for possible interactions with phosphates are in blue and labeled.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 51203-51207) copyright 2004.

Figures were selected by an automated process.