Meta-Biol

• Pathways

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).

Due to the crowded envirnoment within the cell, many proteins must interact with molecular chaperones to attain their native conformation (reviewed in Young et al., 2004). Chaperones recognize and associate with proteins in their non-native state and facilitate their folding by stabilizing the conformation of productive folding intermediates. Chaperones that take part broadly in de novo protein folding, such as the Hsp70s and the chaperonins, facilitate the folding process through cycles of substrate binding and release regulated by their ATPase activity (see Young et al., 2004; Spiess et al., 2004; Bigotti and Clarke, 2008).

Metabolism of proteins, as annotated here, covers the full life cycle of a protein from its synthesis to its posttranslational modification and degradation, at various levels of specificity. Protein synthesis is accomplished through the process of Translation of an mRNA sequence into a polypeptide chain. Protein folding is achieved through the function of molecular chaperones which recognize and associate with proteins in their non-native state and facilitate their folding by stabilizing the conformation of productive folding intermediates (Young et al. 2004). Following translation, many newly formed proteins undergo Post-translational protein modification, essentially irreversible covalent modifications critical for their mature locations and functions (Knorre et al. 2009), including gamma carboxylation, synthesis of GPI-anchored proteins, asparagine N-linked glycosylation, O-glycosylation, SUMOylation, ubiquitination, deubiquitination, RAB geranylgeranylation, methylation, carboxyterminal post-translational modifications, neddylation, and phosphorylation. Peptide hormones are synthesized as parts of larger precursor proteins whose cleavage in the secretory system (endoplasmic reticulum, Golgi apparatus, secretory granules) is annotated in Peptide hormone metabolism. After secretion, peptide hormones are modified and degraded by extracellular proteases (Chertow, 1981 PMID:6117463). Protein repair enables the reversal of damage to some amino acid side chains caused by reactive oxygen species. Pulmonary surfactants are lipids and proteins that are secreted by the alveolar cells of the lung that decrease surface tension at the air/liquid interface within the alveoli to maintain the stability of pulmonary tissue (Agassandian and Mallampalli 2013). Nuclear regulation, transport, metabolism, reutilization, and degradation of surfactant are described in the Surfactant metabolism pathway. Amyloid fiber formation, the accumulation of mostly extracellular deposits of fibrillar proteins, is associated with tissue damage observed in numerous diseases including late phase heart failure (cardiomyopathy) and neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's.