Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding

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Homo sapiens
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The chaperonin complex TRiC/CCT is needed for the proper folding of all five G-protein beta subunits (Wells et al. 2006). TRiC/CCT cooperates with the phosducin-like protein PDCL (commonly known as PhLP or PhLP1), which interacts with both TRiC/CCT and G-protein beta subunits 1-5 (GNB1, GNB2, GNB3, GNB4, GNB5) (Dupre et al. 2007, Howlett et al. 2009). PDCL enables completion of G-protein beta folding by TRiC/CCT, promotes release of folded G-protein beta subunits 1-4 (GNB1, GNB2, GNB3, GNB4) from the chaperonin complex, and facilitates the formation of the heterodimeric G-protein beta:gamma complex between G-protein beta subunits 1-4 and G-protein gamma subunits 1-12 (Lukov et al. 2005, Lukov et al. 2006, Howlett et al. 2009, Lai et al. 2013, Plimpton et al. 2015, Xie et al. 2015). In the case of G-protein beta 5 (GNB5), PDCL stabilizes the interaction of GNB5 with the TRiC/CCT and promotes GNB5 folding, thus positively affecting formation of GNB5 dimers with RGS family proteins (Howlett et al. 2009, Lai et al. 2013, Tracy et al. 2015). However, over-expression of PDCL interferes with formation of GNB5:RGS dimers as PDCL and RGS proteins bind to the same regions of the GNB5 protein (Howlett et al. 2009).

Literature References
PubMed ID Title Journal Year
23637185 Phosducin-like protein 1 is essential for G-protein assembly and signaling in retinal rod photoreceptors

Lai, CW, Kolesnikov, AV, Frederick, JM, Blake, DR, Jiang, L, Stewart, JS, Chen, CK, Barrow, JR, Baehr, W, Kefalov, VJ, Willardson, BM

J. Neurosci. 2013
17363375 Dopamine receptor-interacting protein 78 acts as a molecular chaperone for Ggamma subunits before assembly with Gbeta

Dupré, DJ, Robitaille, M, Richer, M, Ethier, N, Mamarbachi, AM, Hébert, TE

J. Biol. Chem. 2007
16702223 Role of the chaperonin CCT/TRiC complex in G protein betagamma-dimer assembly

Wells, CA, Dingus, J, Hildebrandt, JD

J. Biol. Chem. 2006
19376773 Role of molecular chaperones in G protein beta5/regulator of G protein signaling dimer assembly and G protein betagamma dimer specificity

Howlett, AC, Gray, AJ, Hunter, JM, Willardson, BM

J. Biol. Chem. 2009
16717095 Mechanism of assembly of G protein betagamma subunits by protein kinase CK2-phosphorylated phosducin-like protein and the cytosolic chaperonin complex

Lukov, GL, Baker, CM, Ludtke, PJ, Hu, T, Carter, MD, Hackett, RA, Thulin, CD, Willardson, BM

J. Biol. Chem. 2006
26613416 Stable G protein-effector complexes in striatal neurons: mechanism of assembly and role in neurotransmitter signaling

Xie, K, Masuho, I, Shih, CC, Cao, Y, Sasaki, K, Lai, CW, Han, PL, Ueda, H, Dessauer, CW, Ehrlich, ME, Xu, B, Willardson, BM, Martemyanov, KA

Elife 2015
15889144 Phosducin-like protein acts as a molecular chaperone for G protein betagamma dimer assembly

Lukov, GL, Hu, T, McLaughlin, JN, Hamm, HE, Willardson, BM

EMBO J. 2005
25659125 Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling

Tracy, CM, Kolesnikov, AV, Blake, DR, Chen, CK, Baehr, W, Kefalov, VJ, Willardson, BM

PLoS ONE 2015
25675501 Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assembly

Plimpton, RL, Cuellar, J, Lai, CW, Aoba, T, Makaju, A, Franklin, S, Mathis, AD, Prince, JT, Carrascosa, JL, Valpuesta, JM, Willardson, BM

Proc. Natl. Acad. Sci. U.S.A. 2015
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