G proteins regulate various physiological processes by way of transducing a wide variety of signals ranging from hormonal to sensory stimuli. Malfunctions in G protein signaling lead to numerous diseases. G protein signaling begins with binding of a ligand to a G protein-coupled receptor resulting in a conformational change that leads to the exchange of a GDP for a GTP on G α. The GTP bound α subunit dissociates for its stable Gβγ dimer partner. G α-GTP and Gβγ control the activity of effector enzymes and ion channels that ultimately orchestrate the cellular response to stimulus. Current reports have shown phosducin-like protein (PhLP1) as a co-chaperone with the chaperonin-containing tailless complex polypeptide-1 (CCT) in the assembly of Gβγ dimer. However, the studies did not address the role of PhLP1 and CCT in the translation and eventual assembly of Gβγ dimer. The data presented in Chapter 2 shows a co-translational assembly of Gβγ dimer regulated by PhLP1 and CCT. Chapter 3 discusses the role of PhLP2A and PhLP3 in CCT-mediated assembly of actin and tubulin in mammalian cells. PhLP2 and PhLP3 are members of the phosducin gene family that interact with CCT. Several studies in yeast suggest that PhLP2 promotes CCT-dependent β-actin folding while PhLP3 enhances β-tubulin folding. However, human PhLP2 has been shown to inhibit β-actin folding, indicating that PhLP2 and possibly PhLP3 have very different functions in humans than they do in yeast. As a result, this study investigates in depth the role of PhLP2 and PhLP3 in CCT-dependent β-actin and β-tubulin folding in human cells.



College and Department

Physical and Mathematical Sciences; Chemistry and Biochemistry



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co-translational assembly of G protein betagamma dimer