Dual-Family Peptidylprolyl Isomerases (Immunophilins) of Select Monocellular Organisms

Abstract

The dual-family peptidylprolyl cis-trans isomerases (immunophilins) represent naturally occurring chimera of classical FK506-binding protein (FKBP) and cyclophilin (CYN), connected by a flexible linker, and are found exclusively in monocellular organisms. The modular builds of these molecules represent two distinct types: CYN-(linker)-FKBP and FKBP-3TPR-CYN. Abbreviated respectively as CFBP and FCBP, the two classes also exhibit distinct organism preference, the CFBP being found in prokaryotes, and FCBP, in eukaryotes. This review summarizes the mystery of these unique class of prolyl isomerases, focusing on their host organisms, potential physiological role, and likely routes of evolution.

Protein Tetratricopeptide Repeat and the Companion Non-tetratricopeptide Repeat Helices: Bioinformatic Analysis of Interhelical Interactions

“…Although the structure of this region has not been experimentally determined, secondary and tertiary structure modeling did not reveal any helix. 12,13 Nevertheless, these proteins, expressed recombinantly, are highly soluble. 12,13 Thus, if a downstream companion helix is in fact needed for the solubility of 3TPR modules, the need may be context-dependent, such that in the absence of a companion helix, the presence of other domains in the protein or an abundance of hydrophilic amino acids in the TPR module itself may promote solubility.…”

“…12,13 Nevertheless, these proteins, expressed recombinantly, are highly soluble. 12,13 Thus, if a downstream companion helix is in fact needed for the solubility of 3TPR modules, the need may be context-dependent, such that in the absence of a companion helix, the presence of other domains in the protein or an abundance of hydrophilic amino acids in the TPR module itself may promote solubility. Indeed, the TPR3 modules of the FCBP 3TPRs are exceptionally rich in hydrophilic amino acids, specifically, the acidic amino acid, Asp, and basic amino acids, Arg and Lys, 12,13 which may have obviated the need for a solvation helix.…”

“…12,13 Thus, if a downstream companion helix is in fact needed for the solubility of 3TPR modules, the need may be context-dependent, such that in the absence of a companion helix, the presence of other domains in the protein or an abundance of hydrophilic amino acids in the TPR module itself may promote solubility. Indeed, the TPR3 modules of the FCBP 3TPRs are exceptionally rich in hydrophilic amino acids, specifically, the acidic amino acid, Asp, and basic amino acids, Arg and Lys, 12,13 which may have obviated the need for a solvation helix. It is certainly beyond reason that every helix will need a downstream helix for solubility, because it conjures up the impossible scenario of an ad infinitum chain of helices in a linear protein.…”

“…Overall, the results presented here should generate interest in understanding the exact function of the under-appreciated TPR-companion helices that accompany the majority of TPR domains. If they are indeed specific promoters of solubility, properly matched helices may find applications in biotechnology to express recombinant TPR domains in soluble form 3,5,13,16 without affecting the sequence or functionality of the TPR.…”