Identification of the ligand of Pru p 3, a peach LTP

Cubells-Baeza, Nuria; Gómez‐Casado, Cristina; Tordesillas, Leticia; Ramírez-Castillejo, Carmen; Garrido‐Arandia, María; González‐Melendi, Pablo; Herrero, M.; Pacios, Luis F.; Díaz‐Perales, Araceli

doi:10.1007/s11103-017-0590-z

Cited by 34 publications

(52 citation statements)

References 43 publications

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“…As “complex”, it is referred to the mix of Pru p 3 and its purified ligand (10:1). The ratio was determined by binding assays between Pru p 3 and the lipid‐ligand as previously described . The recombinant Pru p 3 was produced in P Pastoris and isolated using the methods describe by Diaz‐Perales et al (2002) .…”

Section: Methodsmentioning

confidence: 99%

“…However, only 1% of known protein families include allergens and besides, not all the members of those families are allergenic . Although no biochemical feature common to allergenic proteins has been found, more than 50% of allergens have been shown to be lipid carriers, including Bet v 1 (the major allergen of birch pollen) and 2S allergens, which contain a large hydrophobic pocket able to harbour and store many lipid compounds and flavonoids as well . Recently, the ligand of Pru p 3, the peach allergenic lipid transfer protein (LTP), has been identified as a derivative of the alkaloid camptothecin bound to phytosphingosine (Figure A), a lipid tail which is inserted into the Pru p 3 cavity .…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8] Although no biochemical feature common to allergenic proteins has been found, more than 50% of allergens have been shown to be lipid carriers, including Bet v 1 (the major allergen of birch pollen) and 2S allergens, which contain a large hydrophobic pocket able to harbour and store many lipid compounds and flavonoids as well. [8][9][10] Recently, the ligand of Pru p 3, the peach allergenic lipid transfer protein (LTP), has been identified as a derivative of the alkaloid camptothecin bound to phytosphingosine ( Figure 1A), a lipid tail which is inserted into the Pru p 3 cavity. 9 Phytosphingosine is a structural component in membranes, 10 while camptothecin is widely used as a chemotherapeutic agent for its ability to inhibit the enzymatic activity of topoisomerase I.…”

Section: Introductionmentioning

confidence: 99%

“…[8][9][10] Recently, the ligand of Pru p 3, the peach allergenic lipid transfer protein (LTP), has been identified as a derivative of the alkaloid camptothecin bound to phytosphingosine ( Figure 1A), a lipid tail which is inserted into the Pru p 3 cavity. 9 Phytosphingosine is a structural component in membranes, 10 while camptothecin is widely used as a chemotherapeutic agent for its ability to inhibit the enzymatic activity of topoisomerase I. 11 Lipid ligands carried by allergens, or exposed together, might influence the host response to the specific allergen.…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms underlying induction of allergic sensitization by Pru p 3

Tordesillas

Cubells-Baeza

Gómez‐Casado

et al. 2017

Clin Experimental Allergy

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Background Recently, the nature of the lipid-ligand of Pru p 3, one of the most common plant food allergens in Southern Europe, has been identified as a derivative of the alkaloid camptothecin bound to phytosphingosine. However, the origin of its immunological activity is still unknown. Objective We sought to evaluate the role of the Pru p 3 lipid-ligand in the immunogenic activity of Pru p 3. Methods In vitro cultures of different cell types (monocyte-derived dendritic cells (moDCs), PBMCs and epithelial and iNKT-hybridoma cell lines) have been used to determine the immunological capacity of the ligand, by measuring cell proliferation, maturation markers and cytokine production. To study the capacity of the lipid-ligand to promote sensitization to Pru p 3 in vivo, a mouse model of anaphylaxis to peach has been produced and changes in the humoral and basophil responses have been analyzed. Results The lipid-ligand of Pru p 3 induced maturation of moDCsc and proliferation of PBMCs. Its immunological activity resided in the phytosphingosine tail of the ligand. The adjuvant activity of the ligand was also confirmed in vivo, where the complex of Pru p 3-ligand induced higher levels of IgE than Pru p 3 alone. The immunological capacity of the Pru p 3 ligand was mediated by CD1d, as maturation of moDCs was inhibited by anti-CD1d antibodies and Pru p 3-ligand co-localized with CD1d on epithelial cells. Finally, Pru p 3-ligand presented by CD1d was able to interact with iNKTs. Conclusions & Clinical Relevance The Pru p 3 lipid-ligand could act as an adjuvant to promote sensitization to Pru p 3, through its recognition by CD1d receptors. This intrinsic adjuvant activity of the accompanying lipid cargo could be a general essential feature of the mechanism underlying the phenomenon of allergenicity.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mechanisms underlying induction of allergic sensitization by Pru p 3

Tordesillas

Cubells-Baeza

Gómez‐Casado

et al. 2017

Clin Experimental Allergy

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“…A phytosphingosine bound camptothecin derivative was associated with purified peach LTP Pru p 3 and could hence represent an in vivo ligand (25). Nevertheless, the biological relevance of this observation is at present unclear.…”

mentioning

confidence: 95%

Plant lipid transfer proteins: are we finally closing in on the roles of these enigmatic proteins?

Edqvist

Blomqvist

Nieuwland

et al. 2018

Journal of Lipid Research

100

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The nonspecific lipid transfer proteins (LTPs) are small, compact proteins folded around a tunnel-like hydrophobic cavity, making them suitable for lipid binding and transport. LTPs are encoded by large gene families in all land plants, but they have not been identified in algae or any other organisms. Thus, LTPs are considered key proteins for plant survival on and colonization of land. LTPs are abundantly expressed in most plant tissues, both above and below ground. They are usually localized to extracellular spaces outside the plasma membrane. Although the in vivo functions of LTPs remain unclear, accumulating evidence suggests a role for LTPs in the transfer and deposition of monomers required for assembly of the water-proof lipid barriers-such as cutin and cuticular wax, suberin, and sporopolleninformed on many plant surfaces. Some LTPs may be involved in other processes, such as signaling during pathogen attacks. Here, we present the current status of LTP research with a focus on the role of these proteins in lipid barrier deposition and cell expansion. We suggest that LTPs facilitate extracellular transfer of barrier materials and adhesion between barriers and extracellular materials. A growing body of research may uncover the true role of LTPs in plants. Overview of plant non-specific lipid transfer proteinsThe plant non-specific lipid transfer proteins (LTPs) are abundant, secreted, soluble, cysteinerich and small proteins with a molecular size usually below 10 kDa (1, 2). In the LTPs four conserved disulfide bridges, formed by an eight-Cys motif (8CM) with the general form CXn-C-Xn-CC-Xn-CXC-Xn-C-Xn-C, stabilize the folding of four or five α-helices into a very compact 3D-structure (3, 4 and Fig. 1). The folding of the helices results in a central hydrophobic cleft suitable for the binding of hydrophobic ligands, such as fatty acids and other lipids (Fig. 2). The compact structure renders the LTPs very insensitive to heat and denaturing agents (5, 6). LTPs are expressed in all investigated land plants, but have not been detected in any other organisms (7). LTPs are encoded by large gene families in seed plants (2,(8)(9)(10)(11). In bryophytes and ferns the gene families are significantly smaller (7,12). LTPs are classified in five major types (LTP1, LTP2, LTPc, LTPd and LTPg) and four minor types (LTPe, LTPf, LTPh, LTPj and LTPk) (7). The classification is based on the spacing between the Cys residues in the 8CM, the polypeptide sequence identity and the position of evolutionary conserved introns. The classification also reflects post-translational modifications, e.g. LTPs with a GPI-anchor belong to LTPg. LTPd and LTPg are encoded in all land plants which suggests that these were possibly the first LTP types that evolved in land plants. The most well-studied LTP types in flowering plants LTP1 and LTP2 probably evolved later since these are not found in liverworts, mosses or other non-seed plants (7). The LTPs are translated with an N-terminal signal peptide that has a potential to localize th...

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