• Corpus ID: 82557447

The Mechanism of Assembly of the G-Protein Beta Gamma Subunit Dimer by CK2 Phosphorylated Phosducin-Like Protein and the Chaperonin Containing TCP-1

@inproceedings{Baker2006TheMO,
  title={The Mechanism of Assembly of the G-Protein Beta Gamma Subunit Dimer by CK2 Phosphorylated Phosducin-Like Protein and the Chaperonin Containing TCP-1},
  author={Christine M. Baker},
  year={2006}
}
THE MECHANISM OF ASSEMBLY OF THE G-PROTEIN βγ SUBUNIT DIMER BY CK2 PHOSPHORYLATED PHOSDUCIN-LIKE PROTEIN AND THE CHAPERONIN CONTAINING TCP-1 Phosducin-like protein (PhLP) binds G-protein βγ subunits and is thought to assist in assembly of the Gβγ dimer. Phosphorylation of PhLP at serine residues 18-20 by the casein kinase 2 (CK2) appears to play an essential role in this process. PhLP has also been shown to interact with the chaperonin containing TCP-1 (CCT) atop its apical domain, not entering… 

References

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Phosducin‐like protein acts as a molecular chaperone for G protein βγ dimer assembly

A mechanism for G βγ assembly is suggested in which PhLP stabilizes the nascent Gβ polypeptide until Gγ can associate, resulting in membrane binding of Gβγ and release of PhLP to catalyze another round of assembly.

Regulatory interaction of phosducin-like protein with the cytosolic chaperonin complex

Overexpression of PhLP inhibited the ability of CCT to fold newly synthesized β-actin by 80%.

Role of the isoprenyl pocket of the G protein beta gamma subunit complex in the binding of phosducin and phosducin-like protein.

The structural model in which the isoprenyl group escapes contact with the aqueous milieu by inserting into the prenyl pocket and stabilizing the Pdc-binding conformation of Gbetagamma is supported.

Regulation of Phosducin-like Protein by Casein Kinase 2 and N-terminal Splicing*

In intact HEK 293 cells, PhLPS inhibited Gβγ-induced inositol phosphate generation with ∼20-fold greater potency than PhLPL, indicating physiological control of G-protein regulation by PhLP seems to involve phosphorylation by CK2 and alternative splicing of the regulator.

Structure of the complex between the cytosolic chaperonin CCT and phosducin-like protein.

Binding experiments performed with PhLP/Pdc chimeric proteins, taking advantage of the fact that Pdc does not interact with CCT, confirm that both the N- and C-terminal domains of PhLP are involved in CCT binding and that several regions suggested by the docking experiment are indeed critical in the interaction with the cytosolic chaperonin.

Phosducin-like protein regulates G-protein betagamma folding by interaction with tailless complex polypeptide-1alpha: dephosphorylation or splicing of PhLP turns the switch toward regulation of Gbetagamma folding.

It is concluded that the strong inhibitory action of PhLP(S) on Gbetagamma signaling is the result of a previously unrecognized mechanism of Gbetgeamma-regulation, inhibition of G betagamm-folding by interference with TCP-1alpha.

Functional Roles of the Two Domains of Phosducin and Phosducin-like Protein*

Kinetic measurements using surface plasmon resonance showed that phosducin bound Gtβγ with a 2.5-fold greater affinity than phos Ducin-like protein, and most of the free energy of binding comes from the N-terminal domain with a lesser contribution from the C-terminals.

Regulation of Angiotensin II-induced G Protein Signaling by Phosducin-like Protein*

Results of pertussis toxin sensitivity, GTPγS binding, and immunoprecipitation experiments suggest that PhLP inhibits phospholipase Cβ activation by dual mechanisms: steric blockage of G βγ activation of PLCβ and interference with Gβγ-dependent cycling of Gqα by the receptor.