Chaperone molecules protein

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. 

Typically, a series of steps is involved in the work carried out by chaperone molecules. Hsp70 operates on the protein as it is being formed on the ribosome. It recognizes extended or exposed protein chain regions that are more hydrophobic and acts to discourage unwanted association of these parts. It also acts to maintain the growing protein in a somewhat unfolded state. 

SERCA pumps sequester Ca2+ in the ER lumen By maintaining appropriate Ca2+ concentrations in the ER lumen, SERCA pumps also play an essential role in protein synthesis, folding and transport of membrane and secreted proteins. This involves in particular chaperone-dependent processing and post-translational modifications which require a unique calcium rich environment. Chaperone molecules such as calreticulin and calnexin are involved in the quality control pathway in the ER (Berridge, 2002 Ellgaard and Helenius, 2003 Michalak et al., 2002). 

An alternative hypothesis is that ER retention of Z-a,-anti trypsin results in autophagy, specifically of hepatic mitochondria. The basis for this hypothesis is the increase in autophagosomes in cells engineered for inducible expression of Z-tx,-antitrypsin. The mutant protein, along with the chaperone molecule calnexin, can be found in these autophagosomes by immune electron microscopy. It is postulated that mitochondrial dysfunction results from the damage to the mitochondria in the PIZZ liver, leading to the hepatic injury. 

In addition, the cellular localization of certain HDAC subtypes is governed by chaperone proteins (e.g., 14-3-3) which, depending on the phosphorylation state, transport the enzyme from the nucleus to the cytoplasm. Hence, inhibition of interaction with phosphatases, kinases, or chaperone molecules may also provide yet another avenue for regulation of HDAC activity with small-molecule ligands. 

FIGURE 1-31 DNA to RNA to protein. Linear sequences of deoxyribonucleotides in DNA, arranged into units known as genes, are transcribed into ribonucleic acid (RNA) molecules with complementary ribonucleotide sequences. The RNA sequences are then translated into linear protein chains, which fold into their native three-dimensional shapes, often aided by molecular chaperones. Individual proteins commonly associate with other proteins to form supramolecular complexes, stabilized by numerous weak interactions. 

FIGURE 3.8.3 As proteins are formed, chaperone molecules bind to them and assist them to fold in the proper way. These same chaperone molecules can recognize features of improperly folded proteins. Addition or removal of sugar molecules aids in the diagnosis. Incorrectly folded proteins may be either decomposed or fixed. (From Conn, P.M. and Janovick, J.A., Am. Sci., 93, 314, 2005. With permission.)... 

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