Cyclophilins: The Structure and Functions of an Important Peptidyl-prolyl Isomerase

Abstract

Cyclophilins are a subgroup of highly conserved protein family immunophilins which are peptidyl-prolyl isomerases that interconvert between the cis and trans positions. They can act as chaperones in maintaining conformational quality control of proteomes. They are structurally conserved throughout evolution and have been found in mammals, plants, insects, fungi, and bacteria. They share a common fold architecture consisting of 8 antiparallel beta sheets and two alpha helices that pack against the sheets. They exist in the cellular compartment of most tissues and encode special functions. Intracellular Cyclophilins are secreted from cells in response to inflammatory stimuli and can mediate intercellular communication. Pro-inflammatory signals may be stimulated by extracellular Cyclophilin. Overexpression of Cyclophilins can contribute to pathological conditions. Cyclophilins are involved in the pathogenesis of viral infection, neurodegenerative diseases, ageing and cancer. Exhibiting several molecular functions, Cyclophilins can bind to cyclosporine and calcium-dependent ser/thr Calcineurin and has been used to describe the immunosuppressive action of cyclosporine. Cyclophilin can stabilize the cis-trans conformation transition state and speed up isomerization steps in protein folding. This process is important in the assembly of multiple domain proteins. Their existence as foldases and molecular chaperones enable them to be able to assist in the covalent folding or unfolding and the assembly or disassembly of other macromolecular structures.

Cyclophilin BcCyp2 Regulates Infection-Related Development to Facilitate Virulence of the Gray Mold Fungus Botrytis cinerea

“…To determine whether BcCyp2 is a target of CsA, an immunosuppressive agent that binds to the cyclophilin and then inhibits calcineurin [ 11 , 17 ], we tested the sensitivity of the mutant strain Δ Bccyp2 to CsA. Our results demonstrated that conidial germination and hyphal development of the WT strain were dramatically suppressed.…”

“…Second, cyclophilins including BcCyp2 (this study) and Bcp1 [ 17 ] are necessary for CsA inhibition of infection-related development and virulence. In the presence of CsA, the formation of a CsA/cyclophilin complex targets calcineurin and prevents its activity in the regulation of fungal morphogenesis, e.g., hyphal branching/development, infection structure formation [ 11 , 12 , 17 , 21 , 29 ]. Our findings on the differential inhibition of hyphal development, infection structure formation, and host infection in the strains harboring or lacking BcCYP2 in the presence of CsA support this view ( Figure 6 ).…”

“…Cyclophilins (Cyps) are a conserved family of proteins named after their ability of binding to cyclosporin A (CsA), an immunosuppressant used to suppress rejection after internal organ transplants [ 10 , 11 , 12 ]. The cytosolic cyclophilin A is an intracellular receptor of CsA and mediates CsA function in immunosuppression [ 13 ].…”

“…Cyclophilin has the activity of peptidyl-prolyl cis-trans isomerase (PPIase), a rate-limiting enzyme that plays an important role in protein folding and assembly [ 14 , 15 , 16 ]. During the interaction of cyclophilin and CsA, CsA binds to cyclophilin via contact within the hydrophobic pockets and inhibits the PPIase activity [ 11 ]. The resulting cyclophilin/CsA complex is a strong inhibitor of calcineurin (CN, also known as protein phosphatase 2B) [ 17 , 18 ].…”

Protein and phytohormone profiles of Mahanarva spectabilis salivary glands infesting different forages

“…Cypa's efficiency can be compared to HSP90 in terms of its ability to keep the protein in its native form, which guarantees protection against loss of newly synthesized proteins. Peptidyl‐prolyl‐isomerase proteins anchor in proteins involved with splicing to assist in the proper folding of newly synthesized proteins during translation, to keep them organized by avoiding undesirable interactions (Idris et al, 2019).…”