PDBsum entry 1a0r

Complex (transducer/transduction)

PDB id: 1a0r

Contents

Protein chains

340 a.a. *

65 a.a. *

188 a.a. *

Ligands

FAR

Waters ×21

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Phosducin induces a structural change in transducin beta gamma.

Authors

A.Loew, Y.K.Ho, T.Blundell, B.Bax.

Ref.

Structure, 1998, 6, 1007-1019. [DOI no: 10.1016/S0969-2126(98)00102-6]

PubMed id

9739091

Abstract

BACKGROUND: Phosducin binds tightly to the beta gamma subunits (Gt beta gamma) of the heterotrimeric G protein transducin, preventing Gt beta gamma reassociation with Gt alpha-GDP and thereby inhibiting the G-protein cycle. Phosducin-like proteins appear to be widely distributed and may play important roles in regulating many heterotrimeric G-protein signaling pathways. RESULTS: The 2.8 A crystal structure of a complex of bovine retinal phosducin with Gt beta gamma shows how the two domains of phosducin cover one side and the top of the seven-bladed beta propeller of Gt beta gamma. The binding of phosducin induces a distinct structural change in the beta propeller of Gt beta gamma, such that a small cavity opens up between blades 6 and 7. Electron density in this cavity has been assigned to the farnesyl moiety of the gamma subunit. CONCLUSIONS: beta gamma subunits of heterotrimeric G proteins can exist in two distinct conformations. In the R (relaxed) state, corresponding to the structure of the free beta gamma or the structure of beta gamma in the alpha beta gamma heterotrimer, the hydrophobic farnesyl moiety of the gamma subunit is exposed, thereby mediating membrane association. In the T (tense) state, as observed in the phosducin-Gt beta gamma structure, the farnesyl moiety of the gamma subunit is effectively buried in the cavity formed between blades 6 and 7 of the beta subunit. Binding of phosducin to Gt beta gamma induces the formation of this cavity, resulting in a switch from the R to the T conformation. This sequesters beta gamma from the membrane to the cytosol and turns off the signal-transduction cascade. Regulation of this membrane association/dissociation switch of Gt beta gamma by phosducin may be a general mechanism for attenuation of G protein coupled signal transduction cascades.

Figure 3.
Figure 3. Stereo diagrams [41 and 42] of SIGMAA weighted 2F[o]-F[c] maps from round 13 of the refinement. The structure was refined with either (a) a farnesyl (in green) in the pocket (map contoured at 1s) or (b) the water structure (red spheres) from Gaudet et al. [12] (PDB code 2TRC; contoured at 0.8s). The refinement was carried out with the program X-PLOR [33], and included a bulk solvent correction as well as conventional positional refinement. Note that in (b) the waters have moved very little from their starting positions and make good hydrogen bonds with surrounding residues. Only hydrogen bonds between protein residues are shown (dashed lines).

The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 1007-1019) copyright 1998.

Secondary reference #1

Title

Crystal structure at 2.4 angstroms resolution of the complex of transducin betagamma and its regulator, Phosducin.

Authors

R.Gaudet, A.Bohm, P.B.Sigler.

Ref.

Cell, 1996, 87, 577-588. [DOI no: 10.1016/S0092-8674(00)81376-8]

PubMed id

8898209

Figure 4.
Figure 4. Structure of Phosducin(A) Stereo pair showing the Cα trace of phosducin in the complex. The trace for residues 37 to 66 (open bars) is tentative. The N-terminal domain is at the top and the C-terminal domain is at the bottom of the figure. G[t]βγ would be located to the right of the N-terminal domain. The Ser-73 α carbon is enlarged and labeled. This figure was generated by DPLOT (G. Van Duyne).(B) Stereo pair showing the least-squares superimposed Cα traces of the phosducin C-terminal domain (blue) and thioredoxin ([18]) (red). The N- and C-terminal residues of the C-terminal domain are labeled P111 and P230, respectively. The N- and C-terminus of thioredoxin are labeled T1 and T108. The C-terminal domain is viewed from its left side, relative to (A), in an orientation similar to that in Figure 6A.

Figure 8.
Figure 8. Electrostatic Potential Representation of Phosducin/G[t]βγ and G[t]βγ AloneElectrostatic potential contoured at +1.5 kT (blue) and −1.5 kT (red) (ionic STRENGTH = 100 mM). On the left is the phosducin/G[t]βγ complex, in the same orientation as in Figure 6A. On the right is G[t]βγ alone, in the same orientation. This figure was generated using GRASP ([33]).

The above figures are reproduced from the cited reference with permission from Cell Press

Secondary reference #2

Title

The structure of the g protein heterotrimer gi alpha 1 beta 1 gamma 2.

Authors

M.A.Wall, D.E.Coleman, E.Lee, J.A.Iñiguez-Lluhi, B.A.Posner, A.G.Gilman, S.R.Sprang.

Ref.

Cell, 1995, 83, 1047-1058. [DOI no: 10.1016/0092-8674(95)90220-1]

PubMed id

8521505