Formation during protein folding

Protein disulfide isomerase and Erolp are enzymes that help form disulfide bonds within the endoplasmic reticulum. These factors are critical for the normal formation of disulfide bonds during protein folding. See Lodi, T., Neglia, B., and Donnini, C., Secretion of human serum albumin by... 

Immunoglobulin (Ig) light chains are responsible for quite a few protein deposition diseases. Some immunoglobulin chains form amyloid deposits, whereas others do not. A protein conformational change in the partially folded protein is involved that subsequently leads to association and fibril formation. During the folding pathway of especially larger proteins, hydrophobic patches may be exposed. ... 

Formation of Incorrect Disulfide Bridges and Reshuffling Processes during Protein Folding... 

Enzymes assist formation of proper disulfide bonds during folding Isomerization of proline residues can be a rate-limiting step in protein folding Proteins can fold or unfold inside chaperonins GroEL is a cylindrical structure with a... 

As discussed earlier in this chapter and also in chapter 6, thermal stabilities of proteins in vivo are influenced by many constituents of the intracellular milieu, including low-molecular-mass protein stabilizers. The process of protein folding, whether during initial synthesis or following heat-induced unfolding, thus will be influenced not only by activities of protein chaperones, but also by the activities of low-mole-cular-mass organic solutes. In principle, heat stress could be ameliorated in part by accumulation of low-molecular-mass protein-stabilizing solutes that favor formation of the compact, folded state of proteins. Such chemical chaperones could complement the activities of protein chaperones. 

The formation of stable secondary structures and a unique tertiary structure of proteins are dictated by the interactions between constituent amino acid residues along the polypeptide chain and by their interactions with the surrounding medium. During the process of protein folding, the hydrophobic force drives the polypeptide chain to the folded state and overcomes the entropic factors while hydrogen bonds, ion pairs, disulhde bonds, and van der Waals interactions define the shape and keep it from falling apart. The structure of a protein mainly dictates its function, and the attainment of stable conformation is essential for proper function. Hence, many methods have been developed to determine the three-dimensional structures of proteins experimentally. 

Formation of IBs during protein expression poses a bottleneck in the efficient downstream processing of therapeutic proteins. The reasons for IB formation are not fully known. Because translation is a slower process than protein folding, it is likely that the misfolding of translation intermediates plays some role. Further, since post-translational modifications, such as glycosylation and lyposylation, which are known to affect the secondary structure of proteins, are absent in bacteria, the non-modified protein structure may cause misfolding. The recovery of soluble... 

The common features of protein folding that emerge from our studies and those in the literature are the importance of initial formation of mixed disulfides, which appear to promote intramolecular disulfides, and the continued presence of a reducing agent to allow disruption of any incorrect disulfide bonds that form during the process. In addition, our protein appears to require the reducing agent to prevent the formation of an oxidized variant. Chan (8) has reported on the necessity of a protonated amine on the mixed disulfide for... 

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