Peptidyl-prolyl Cis/trans Isomerase Activity In The Functioning Of Native Folded Proteins

The finding that cis/trans isomerization of proline pept ide bonds can prov ide the basis for conformational changes in native folded proteins, ensuring transition between functionally different states, has led to marked progress in this field of research. Presently, there are reasons to assume that the proline switch can serve as a precise regulator of biological function in native folded proteins. This review aims to summarize the available information on proline switch mechanisms in different proteins, focusing the attention on features pointing to similarities or distinctions between these mechanisms. Two groups of proteins are considered. The first one includes proteins which require the presence of an external factor accelerating the process of isomerization. These proteins are interleukin2 tyrosine kinase SH2 domain and the Crk adaptor protein. Each of them is able to catalyze an intrinsic intramolecular switch afforded by prolyl cis/trans isomerization, but this process is very slow; it can, however, be significantly accelerated by cyclophilin A (CypA), a peptidyl-prolyl cis/trans isomerase. The second group, comprising 5HT3 receptor of neurotransmitter-gated ion channel, cytochrome P450cam, and molecular chaperone Hsp70, can do without external catalysts; these proteins are able to accelerate cis/trans isomerization due to intrinsic structural features that facilitate this process. In each case, the likely mechanism of proline switch is discussed. Special attention is given to the possibility that a conformational switch may result from a shift of equilibrium between coexisting cis and trans conformers.