Current Understanding of the Structure and Function of Fungal Immunomodulatory Proteins

Abstract

Fungal immunomodulatory proteins (FIPs) are a group of proteins found in fungi, which are extensively studied for their immunomodulatory activity. Currently, more than 38 types of FIPs have been described. Based on their conserved structure and protein identity, FIPs can be classified into five subgroups: Fve-type FIPs (Pfam PF09259), Cerato-type FIPs (Pfam PF07249), PCP-like FIPs, TFP-like FIPs, and unclassified FIPs. Among the five subgroups, Fve-type FIPs are the most studied for their hemagglutinating, immunomodulating, and anti-cancer properties. In general, these small proteins consist of 110-125 amino acids, with a molecular weight of ∼13 kDa. The other four subgroups are relatively less studied, but also show a noticeable influence on immune cells. In this review, we summarized the protein modifications, 3-dimensional structures and bioactivities of all types of FIPs. Moreover, structure-function relationship of FIPs has been discussed, including relationship between carbohydrate binding module and hemagglutination, correlation of oligomerization and cytokine induction, relevance of glycosylation and lymphocyte activation. This summary and discussion may help gain comprehensive understanding of FIPs' working mechanisms and scope future studies.

The Enhancing Effect of Fungal Immunomodulatory Protein-Volvariella Volvacea (FIP-vvo) on Maturation and Function of Mouse Dendritic Cells

“…A lot of studies indicate that Fve-type FIPs can regulate innate and adaptive immunity. In contrast, the other four subgroups of FIPs mainly modulate innate immune responses, for example, macrophage activity [ 5 ]. In fact, Fve-type FIPs from different fungus species have various abilities of immune regulation, and they even share structure homology.…”

“…The low yield of FIPs is the main limitation for research and application. The production of recombinant FIP through gene cloning technology has greatly improved the quantity and quality of FIP [ 5 ]. In this study, the recombinant FIP-vvo proteins can enhance DC maturation and function the same as the natural FIP-vvo.…”

“…(3) PCP-like FIPs, which are classified by protein identity (Poria cocos immunomodulatory protein, PCP); (4) TFP-like FIP, which only contains Tremella fuciformis protein (TFP); and (5) unclassified FIP [5]. In 1997, Hsu et al purified a protein from V. volvacea known as FIP-vvo [6].…”

“…A group of proteins have been isolated from various fungi with conservative structures, and they form a family named fungal immunomodulatory proteins (FIPs). FIPs can be divided into five subgroups: (1) Fve-type FIPs, which have the Fve family ( Flammulina velutipes ) domain signature (Pfam: PF09259); (2) Cerato-type FIPs, which contain the cerato-platanin family ( Ascomycete Ceratocystis platani ) domain signature (Pfam: PF07249); (3) PCP-like FIPs, which are classified by protein identity ( Poria cocos immunomodulatory protein , PCP); (4) TFP-like FIP, which only contains Tremella fuciformis protein (TFP); and (5) unclassified FIP [ 5 ]. In 1997, Hsu et al purified a protein from V. volvacea known as FIP-vvo [ 6 ].…”

GMI, an Immunomodulatory Peptide from Ganoderma microsporum, Restrains Periprosthetic Joint Infections via Modulating the Functions of Myeloid-Derived Suppressor Cells and Effector T Cells

“…These compounds are considered safer and less toxic than the synthetic drugs [21,22]. Fungal immunomodulatory proteins (FIPs) are a group of peptides, which are known to modulate immunity [23,24]. So far, 38 types of FIPs have been identified, which are classified into five subgroups [24].…”