PDBsum entry 1b9x

Signaling protein

PDB id: 1b9x

Contents

Protein chains

340 a.a. *

68 a.a. *

169 a.a. *

Metals

_GD ×6

Waters ×18

* Residue conservation analysis

References listed in PDB file

Key reference

Title

A molecular mechanism for the phosphorylation-Dependent regulation of heterotrimeric g proteins by phosducin.

Authors

R.Gaudet, J.R.Savage, J.N.Mclaughlin, B.M.Willardson, P.B.Sigler.

Ref.

Mol Cell, 1999, 3, 649-660. [DOI no: 10.1016/S1097-2765(00)80358-5]

PubMed id

10360181

Abstract

Visual signal transduction is a nearly noise-free process that is exquisitely well regulated over a wide dynamic range of light intensity. A key component in dark/light adaptation is phosducin, a phosphorylatable protein that modulates the amount of transducin heterotrimer (Gt alpha beta gamma) available through sequestration of the beta gamma subunits (Gt beta gamma). The structure of the phosphophosducin/Gt beta gamma complex combined with mutational and biophysical analysis provides a stereochemical mechanism for the regulation of the phosducin-Gt beta gamma interaction. Phosphorylation of serine 73 causes an order-to-disorder transition of a 20-residue stretch, including the phosphorylation site, by disrupting a helix-capping motif. This transition disrupts phosducin's interface with Gt beta gamma, leading to the release of unencumbered Gt beta gamma, which reassociates with the membrane and Gt alpha to form a signaling-competent Gt alpha beta gamma heterotrimer.

Figure 4.
Figure 4. One-Dimensional Proton NMR of the N-Terminal Domain(A and C) Amide region.(B and D) Methylene region.The spectrum of the phosphorylated N-terminal domain is shown at the top (A and B) and that of the unphosphorylated N-terminal domain is at the bottom (C and D). Arrows point to spectral features that differ between the two forms of the domain.

Figure 6.
Figure 6. Interactions of Phospho-Phosducin and G[t]α with G[t]βγ(A) Ribbon diagram of the phosducin/G[t]βγ complex where residues 67–86, which become disordered upon Ser-73 phosphorylation, are colored cyan. The N-terminal domain of phosducin is purple, with its 30-residue flexible loop in green. The C-terminal domain is blue. G[t]β is gold, and G[t]γ is silver.(B) The transducin heterotrimer ([14]) with G[t]α in red, the GDP in black, and G[t]βγ colored as in (A). Residues 67–86 in phosducin overlap the G[t]α-G[t]βγ interaction surface.(C) Ribbon diagram (stereo pair) of the phosducin/G[t]βγ interface near Helix 2. Residues involved in the interactions with phosducin segment from Arg-67 to Asp-86 are shown in ball-and-stick representations. Phosducin residues are labeled with purple or cyan symbols, and G[t]βγ residues with black symbols. The complex is viewed in the same “top” orientation in all three panels.

The above figures are reprinted by permission from Cell Press: Mol Cell (1999, 3, 649-660) copyright 1999.

Secondary reference #1

Title

Crystal structure of a g-Protein beta gamma dimer at 2.1a resolution.

Authors

J.Sondek, A.Bohm, D.G.Lambright, H.E.Hamm, P.B.Sigler.

Ref.

Nature, 1996, 379, 369-374.

PubMed id

8552196