Lipid chaperone

The FABPs are a family of carrier proteins for fatty acids and other lipophilic substances, such as eicosanoids and retinoids. These proteins are thought to facilitate the transfer of fatty acids between extra- and intracellular membranes. Adipocyte fatty acid-binding protein (aP2 FABP4) is expressed in adipocytes and macrophages, and integrates inflammatory and metabolic responses. Studies in aP2-deflcient mice have shown that this lipid chaperone has a significant role in several aspects of the metabolic syndrome, including type 2 diabetes and atherosclerosis. FABP has also been introduced as a plasma marker of acute myocardial infarction. 

Lipid chaperone A lipid that modulates the conformation, and thus the function, of a membrane protein. Cholesterol and sphingolipids are typical chaperone lipids. 

The general types of protein-protein interactions that occur in cells include receptor-ligand, enzyme-substrate, multimeric complex formations, structural scaffolds, and chaperones. However, proteins interact with more targets than just other proteins. Protein interactions can include protein-protein or protein-peptide, protein-DNA/RNA or protein-nucleic acid, protein-glycan or protein-carbohydrate, protein-lipid or protein-membrane, and protein-small molecule or protein-ligand. It is likely that every molecule within a cell has some kind of specific interaction with a protein. 

The most extensively studied TRIAD is Parkin, shown schematically in Figure 4.5A. The N-terminus contains a region homologous to ubiquitin called the ubiq-uitin domain (UbD), which interacts directly with proteasomes. The C-terminus contains two RING fingers (Rl, R2) separated by a cysteine-rich in-between i ING (IBR) region. This TRIAD motif mediates E3 activity and interacts with molecular chaperones. The last three amino acids of Parkin interact with a PDZ domain and possibly function to anchor Parkin to lipid microdomains. 

For Ras proteins, there is no chaperone protein available or known to solubilize the lipidated protein thus the refolding of, for example, lipidated N- and H-Ras is not feasible. However, lipidated K-Ras 110 can be generated via expressed protein ligation (EPL), since the polybasic C-terminal region of this protein helps to solubilize the protein even when farnesylated and facilitates the purification (Scheme 36). ... 

Metalloprotein protein that binds a specific metal ion and requires that metal ion for proper function Metal transporter transmembrane protein responsible for the translocation of metal ions across a lipid bilayer MTMl mitochondrial inner membrane transporter needed for activating SOD2 with manganese SCO Copper carrying molecule, possibly the copper chaperone or copper insertion factor for cytochrome oxidase SMF2 intracellular metal transporter essential for manganese trafficking... 

Temperature and pressure extremes require different strategies. Cellular lipids, proteins and nucleic acids are sensitive to high temperatures. Hyperthermophile bacteria have ether lipids instead of the more hydrolysis sensitive ester lipids in mesophiles [13]. Enzymes from hyperthermophiles show an unusual thermostability in the laboratory, and an important aspect of protein chemistry research is to find out the stabilizing principles. Crude cell extracts of hyperthermophiles show the presence of heat inducible proteins, called chaperones, which assist in the folding of proteins during cellular synthesis. Molecular details for cold adaptation of enzymes have been reported but are less extensively studied [14]. 

Molecular chaperones, traditionally proteins, facilitate the folding of proteins by interacting non-covalently with non-native folding intermediates and not with either the native or totally unfolded protein. When folding is complete, molecular chaperones are not required to maintain proper conformation. However, molecular chaperone function is not restricted to proteins (Bogdanov et ah, 1996 Ellis, 1997). Specific lipids are able to interact with partially folded proteins in a transient manner in either de novo protein folding or protein renaturation in vitro similar to that of protein molecular chaperones. 

Based on all these results lipids can function as non-protein molecular chaperones or lipochaperones that specifically mediate the folding of proteins thereby extending the definition of chaperones to other biomolecules in addition to proteins (Bogdanov and Dowhan, 1999). 

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