Prediction of Disordered Regions and Their Roles in the Anti-Pathogenic and Immunomodulatory Functions of Butyrophilins

Abstract

Butyrophilins (BTNs) are a group of the moonlighting proteins, some members of which are secreted in milk. They constitute a large family of structurally similar type 1 transmembrane proteins from the immunoglobulin superfamily. Although the founding member of this family is related to lactation, participating in the secretion, formation and stabilization of milk fat globules, it may also have a cell surface receptor function. Generally, the BTN family members are known to modulate co-stimulatory responses, T cell selection, differentiation, and cell fate determination. Polymorphism of these genes was shown to be associated with the pathology of several human diseases. Despite their biological significance, structural information on human butyrophilins is rather limited. Based on their remarkable multifunctionality, butyrophilins seem to belong to the category of moonlighting proteins, which are known to contain intrinsically disordered protein regions (IDPRs). However, the disorder status of human BTNs was not systematically investigated as of yet. The goal of this study is to fill this gap and to evaluate peculiarities of intrinsic disorder predisposition of the members of human BTN family, and to find if they have IDPRs that can be attributed to the multifunctionality of these important proteins.

Dysfunctional BTN3A together with deregulated immune checkpoints and type I/II IFN dictate defective interplay between pDCs and γδ T cells in melanoma patients, which impacts clinical outcomes

“… 67 In addition, the recent discovery that BTN2A1 plays a critical role in PAg recognition by γδ T cells by binding the γδ TCR in conjunction with BTN3A1 68 sustain even more the rationale to study deeply the BTN family of molecules both on tumor cells and immune infiltrating cells to elucidate the mechanism of BTN3A dysfunction in melanoma. Besides, it has been highlighted that the polymorphism of genes coding for BTNs is associated with pathologies in humans 69 especially cancers. A positive association between BTN3A2 expression, higher T‐cell infiltration and better prognosis has been pointed out in ovarian cancer 70 and breast cancer, 71 suggesting that BTN3A2 expression in tumor microenvironment modulates the density and nature of immune infiltration.…”

Comparative Analysis of Milk Fat Globular Membrane (MFGM) Proteome between Saudi Arabia Camelus dromedary Safra and Wadha Breeds

“…Butyrophilin is one of the most abundant MFGM proteins expressed in lactating mammary glands and is a major component of MFGM [47]. BTN is a member of the B7-like proteins family and is encoded by a single gene located telomeric to the HLA complex [48] consisting of two extracellular immunoglobulin domains constant IgC, and variable IgV and a transmembrane region [47]. It is Figure 6.…”

“…Butyrophilin is one of the most abundant MFGM proteins expressed in lactating mammary glands and is a major component of MFGM [47]. BTN is a member of the B7-like proteins family and is encoded by a single gene located telomeric to the HLA complex [48] consisting of two extracellular immunoglobulin domains constant IgC, and variable IgV and a transmembrane region [47]. It is considered as immune system regulator due to is present in immune cells such as lymphocytes, macrophages, monocytes and others [49] and is expressed by thymic stromal cells and inhibits proliferation and cytokine production of stimulated CD4+ and CD8+ T cells [32].…”

High‐throughput prediction of disordered moonlighting regions in protein sequences

“…The disordered moonlighting regions (DMRs) are different from moonlighting proteins since they concern regions rather than complete protein chains and since they focus specifically on the intrinsic disorder. Recent research has revealed many examples of diverse and functionally important DMRs . Although many DMRs can be found in the DisProt database, a significantly larger number of these regions is awaiting to be discovered.…”

“…Recent research has revealed many examples of diverse and functionally important DMRs. [39][40][41][42] Although many DMRs can be found in the DisProt database, a significantly larger number of these regions is awaiting to be discovered. Computational prediction of DMRs is necessary to find these regions among the large and growing number of IDRs.…”