Protein folding inside

Ellis, R.J. (1996a). The bio in biochemistry Protein folding inside and outside the cell. Science 272 1448-1449. 

Anyone aware of the similar biochemical functions of hemoglobin, myoglobin, and leghemoglobin could expect the structural similarities. In a growing number of other cases, however, a comparison of three-dimensional structures has revealed striking similarities between proteins that were not expected to be related. A case in point is the protein actin, a major component of the cytoskeleton (Section 34.2), and heat shock protein 70 (Hsp-70), which assists protein folding inside cells. These two proteins were found to be noticeably similar in structure despite only 1.5.6% sequence identity (Figure 6.15). On the basis of their three-dimensional structures,... 

The "bio" in biochemistry protein folding inside and outside the cell, R. J. Ellis, 1996, Science, 272 14481449. 

Before protein molecules attain their native folded state they may expose hydrophobic patches to the solvent. Isolated purified proteins will aggregate during folding even at relatively low protein concentrations. Inside cells, where there are high concentrations of many different proteins, aggregation could therefore occur during the folding process. This is prevented by... 

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... 

The van der Waals model of monomeric insulin (1) once again shows the wedge-shaped tertiary structure formed by the two chains together. In the second model (3, bottom), the side chains of polar amino acids are shown in blue, while apolar residues are yellow or pink. This model emphasizes the importance of the hydrophobic effect for protein folding (see p. 74). In insulin as well, most hydrophobic side chains are located on the inside of the molecule, while the hydrophilic residues are located on the surface. Apparently in contradiction to this rule, several apolar side chains (pink) are found on the surface. However, all of these residues are involved in hydrophobic interactions that stabilize the dimeric and hexameric forms of insulin. 

It should be noted that liposomes in effect mimic cell walls and proteins are to be found in nature associated with cell walls. However, the association may differ physical according to the conformation for the protein under consideration. For example some proteins fold so that they are exposing hydrophobic regions which lit into the hydrophobic regions of the liposomal structure (or cell wall). The net effect is that the transbilayer protein exposes its hydrophilic regions both inside and outside of the liposomal structure to the water surrounding the structure (Figure 9.6). 

How does the hydrophobic effect favor protein folding Some of the amino acids that make up proteins have nonpolar groups. These nonpolar amino acids have a strong tendency to associate with one another inside the interior of the folded protein. The increased entropy of water resulting from the interaction of these hydrophobic amino acids helps to compensate for the entropy losses inherent in the folding process. 

Recent reports on facilitation of protein folding by molecular chaperones 46-48) provide another possibility the difference between these two pathways could be a consequence of lack of certain cellular components in the in vitro reaction. It was observed that the products of gr< -bearing plasmid were able to rescue some temperature sensitive P22 tailspike mutants in Salmonella at the restrictive temperature (39 C), though very weakly 49), On the other hand, high yield of the native protein was also reported in the refolding (reconstitution) of the acid urea denatured tailspike polypeptide chains without the addition of cellular factors at low temperatures (10°C) (57). This in vitro result indicates that auxiliary factors inside the cell are not absolutely required for the folding of this protein, at least under these experimental conditions. However, this does not rule out that the cellular factors could play a role under in vivo conditions. 

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