Helper protein

Most reactions in cells are carried out by enzymes [1], In many instances the rates of enzyme-catalysed reactions are enhanced by a factor of a million. A significantly large fraction of all known enzymes are proteins which are made from twenty naturally occurring amino acids. The amino acids are linked by peptide bonds to fonn polypeptide chains. The primary sequence of a protein specifies the linear order in which the amino acids are linked. To carry out the catalytic activity the linear sequence has to fold to a well defined tliree-dimensional (3D) stmcture. In cells only a relatively small fraction of proteins require assistance from chaperones (helper proteins) [2]. Even in the complicated cellular environment most proteins fold spontaneously upon synthesis. The detennination of the 3D folded stmcture from the one-dimensional primary sequence is the most popular protein folding problem. 

Disulfide bonds are hardly formed in cytosol of unmodified E. coli strains. Such enzymes can be expressed in E. coli Origami strain, in cells coexpressing helper proteins, such as PDI or DsbC, or they can be directed to the more oxidative periplasm. 

Only correctly folded proteins can perform their biological function correctly. This complicated process is currently under active investigation a whole class of folding helper proteins, the chaperones [2], are used by Nature to prevent misfolding events with their often dramatic consequences (TSE, Alzheimer s disease, etc., vide infra). 

Chaperones are needed for nucleic acids as well as proteins. The concept that the proper folding of macromolecules may depend on the activities of helper proteins—molecular chaperones—has recently been extended to nucleic acids, notably RNA. As pointed out above, the formation of secondary structures in nucleic acids is an exothermic process (AH is negative), and thus favored by reductions in temperature. If temperature decreases to very low values, nucleic acids may acquire too high a stability of native secondary structure to function well. Moreover, additional regions of secondary structure may form that disrupt normal functions such as transcription and translation. 

Thus, the common factor underlying aggregate formation is failure of partially folded intermediates to correctly proceed through the productive pathway. This may result from their partial intracellular denaturation, due for example to temperature, or lack of proper environmental conditions. Absence of necessary cofactors and helper proteins, or failure to interact with them at a critical stage may also result in aggregation of folding intermediates as depicted in Figure 5. 

In many cases, refolding to the native state is incomplete or not precise. For many proteins, the peptide chain produced in the cell assumes its native folded state with the aid of specific helper proteins, called chaperonins. These are missing when a protein has been denatured and is allowed to refold in practice. Several proteins refold into a near-to-native state, which then may or may not slowly change into the native conformation. 

Some of these helper proteins such as UreE and HybB bind the nickel cations meant for incorporation into nickel-containing enzymes (Lee et al. 1993, Park et al. 1994, Lee etal., 2002b, Song etal. 2001, Remaut etal. 2001). These proteins act as metal chaperones, which discriminate between anabolic nickel that serves as a trace element and toxic nickel. Ni(II) binds to polyphosphate, like many other divalent cations (Gonzalez and Jensen 1998), but... 

Jansen, R. et al. (2013) Concerted action of P450 plus helper protein to form the amino-hydroxy-piperidone moiety of the potent protease inhibitor crocapeptin. /. Am. Chem. Soc., 135 (45), 16885-16894. 

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