Plant and Arthropod IgE-Binding Papain-like Cysteine Proteases: Multiple Contributions to Allergenicity

Abstract

Papain-like cysteine proteases are widespread and can be detected in all domains of life. They share structural and enzymatic properties with the group's namesake member, papain. They show a broad range of protein substrates and are involved in several biological processes. These proteases are widely exploited for food, pharmaceutical, chemical and cosmetic biotechnological applications. However, some of them are known to cause allergic reactions. In this context, the objective of this review is to report an overview of some general properties of papain-like cysteine proteases and to highlight their contributions to allergy reactions observed in humans. For instance, the literature shows that their proteolytic activity can cause an increase in tissue permeability, which favours the crossing of allergens through the skin, intestinal and respiratory barriers. The observation that allergy to PLCPs is mostly detected for inhaled proteins is in line with the reports describing mite homologs, such as Der p 1 and Der f 1, as major allergens showing a frequent correlation between sensitisation and clinical allergic reactions. In contrast, the plant food homologs are often digested in the gastrointestinal tract. Therefore, they only rarely can cause allergic reactions in humans. Accordingly, they are reported mainly as a cause of occupational diseases.

Keywords: allergen homologs; gastrointestinal digestion; inhaled allergens; mite proteases; occupational allergy; plant food; proteolytic activity; sensitisation; tight junction; tissue permeabilisation.

Figure 1

Sources of plant food PLCPs and exposure routes. The diagram shows the fruits (on the left) known as sources of the reported PLCPs (in between), which find several industrial applications (on the right).

Figure 2

Diagram showing possible sources of commonly inhaled PLCPs and the exposure routes.

Figure 3

Schematic representation of some properties of PLCPs. Panel (A): summary of PLCP activities. Panel (B): 3D model of papain performed on the Expasy Swiss Bioinformatics Resource Portal (www.expasy.org/resources/swiss-model, accessed on 2 January 2024) by submitting the papain sequence with Uniprot code P00784.

Figure 4

Schematic representation of a model of the complex PLCP substrate proposed by Schechter and Berger [48]. The binding cleft of the enzyme is composed of seven subsites, indicated as S1–S4 and S1′–S3′, located on both sides of the catalytic site. The enzyme cleavage site (ECS) is shown. The positions, P1–P4 and P1′–P3′, on the substrate are counted from the cleavage point with the same numbering as the subsites of the enzyme they occupy.

Figure 5

Schematic representation of the proteolytic activity of PLCPs on the epithelial tissues. Normal (on the (left)) and damaged (on the (right)) epithelia are shown. Protein molecules are represented by squares, triangles and rhombuses. Allergenic proteins are shown as circles.

Figure 6

Schematic representation of three possible events (I, II and III) that can affect the contribution of PLCPs to allergenicity.