Calcium–Binding Allergens: From Plants to Man

Valenta, Rudolf; Hayek, Brigitte; Seiberler, Susanne; Bugajska-Schretter, Agnes; Niederberger, Verena; Twardosz, Anna; Natter, Susanne; Vangelista, Luca; Pastore, Annalisa; Spitzauer, Susanne; Kraft, Dietrich

doi:10.1159/000024005

Cited by 106 publications

(93 citation statements)

References 33 publications

(64 reference statements)

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“…Third, we have experimentally excluded a role for CaM. Fourth, although EF-hand motifs are present in numerous proteins that play a role in various cellular processes (39), most of these are localized intracellularly. The observation that our target is located extracellularly narrows the list of possible candidates and mainly leaves us with the integrins.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Very Late Antigen-5-Mediated Adhesion of Bone Marrow-Derived Mast Cells to Fibronectin by Peptides with Inverted Hydropathy to EF-Hands

Broeke

Blalock

Villain

et al. 2001

The Journal of Immunology

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Release of allergic mediators from mast cells is enhanced by very late Ag (VLA)-5-mediated interaction of these cells with fibronectin. In this report, we show that VLA-5-mediated adhesion of bone marrow-derived mast cells to fibronectin can be induced by two different pathways: first, FcεRI clustering, which depends on calmodulin activation and extracellular Ca2+, and, second, by Mn2+ stimulation, which is independent of calmodulin activation and antagonized by Ca2+. Previous studies have shown the presence of several cation-binding domains in VLA-5 that are homologous to the calcium-binding EF-hands of calmodulin. To show a role for EF-hands of different proteins in VLA-5-mediated adhesion, we used calcium-like peptides (CALP), CALP1 and CALP2, designed to bind to EF-hands based on inverted hydropathy. CALP1 and, more potently, CALP2 inhibited FcεRI-induced adhesion to fibronectin via different mechanisms. The target for the effects of CALP1 and 2 on FcεRI-induced adhesion and degranulation was intracellular and likely involved calmodulin. Interestingly only CALP2 was able to inhibit Mn2+-induced calmodulin-independent adhesion by interfering with an extracellular target, which is probably VLA-5. We conclude that CALP1 and 2 can inhibit VLA-5-mediated adhesion of mast cells to fibronectin through binding to EF-hands of multiple proteins, and that these peptides can be used as lead compounds for the development of future therapy against allergy.

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Section: Discussionmentioning

confidence: 99%

Attenuation of Very Late Antigen-5-Mediated Adhesion of Bone Marrow-Derived Mast Cells to Fibronectin by Peptides with Inverted Hydropathy to EF-Hands

Broeke

Blalock

Villain

et al. 2001

The Journal of Immunology

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“…22 These polcalcins share more than 65% sequence identity with Bet v 4 ( Figure 1) and due to their widespread distribution over the plant kingdom and their high IgE cross-reactivity 10 -13,17,19 -21 they might constitute so-called panallergens. 23 The polcalcins, whose physiological function is still unknown, are specifically expressed in anthers and pollen 10,14,15,17 -21,24,25 and therefore no IgE cross-reactive food allergens have been described. , Ole e 3 (79.5%), Syr v 3 (77.5%), Bra n 1 (74.4%), Bra n 2 (73.2%), Phl p 7 (68.8%), Cyn d 7 (68.4%), the NH 2 -terminal (36.6%) as well as the COOH-terminal (41.5%) domain of calmodulin from Homo sapiens, the NH 2 -terminal (35.5%) as well as the COOH-terminal (34.3%) domain of troponin C from Gallus gallus, parvalbumin from Cyprinus carpio (27.8%), and calbindin D 9k from Bos taurus (27.4%).…”

Section: Introductionmentioning

confidence: 99%

Solution Structure, Dynamics, and Hydrodynamics of the Calcium-bound Cross-reactive Birch Pollen Allergen Bet v 4 Reveal a Canonical Monomeric Two EF-Hand Assembly with a Regulatory Function

Neudecker

Nerkamp

Eisenmann

et al. 2004

Journal of Molecular Biology

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Birch pollinosis is one of the prevailing allergic diseases. In all, 5 -20% of birch pollinotics mount IgE antibodies against the minor birch pollen allergen Bet v 4, a Ca 2þ -binding polcalcin. Due to IgE cross-reactivity among the polcalcins these patients are polysensitized to various plant pollens. Determination of the high-resolution structure of holo Bet v 4 by heteronuclear NMR spectroscopy reveals a canonical two EF-hand assembly in the open conformation with interhelical angles closely resembling holo calmodulin. The polcalcin-specific amphipathic COOH-terminal a-helix covers only a part of the hydrophobic groove on the molecular surface. Unlike the polcalcin Phl p 7 from timothy grass, which was recently shown to form a domain-swapped dimer, the hydrodynamic parameters from NMR relaxation, NMR translational diffusion, and analytical ultracentrifugation indicate that both apo and holo Bet v 4 are predominantly monomeric, raising the question of the physiological and immunological significance of the dimeric form of these polcalcins, whose physiological function is still unknown. The reduced helicity and heat stability in the CD spectra, the poor chemical shift dispersion of the NMR spectra, and the slightly increased hydrodynamic radius of apo Bet v 4 indicate a reversible structural transition upon Ca 2þ binding, which explains the reduced IgE binding capacity of apo Bet v 4. The remarkable structural similarity of holo Bet v 4 and holo Phl p 7 in spite of different oligomerization states explains the IgE cross-reactivity and indicates that canonical monomers and domain-swapped dimers may be of similar allergenicity. Together with the close structural homology to calmodulin and the hydrophobic ligand binding groove this transition suggests a regulatory function for Bet v 4.

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“…Likewise, proteins with calcium-binding capacities include a conserved motif in common. These proteins were indeed proved to form a group of pan-allergens (Valenta et al, 1998). What, then, is the pan-allergen responsible for latex-fruit syndrome?…”

Section: Cross-reactive Plant Allergensmentioning

confidence: 99%

Features and Mode of Action of Cross-reactive Plant Allergens Relevant to Latex-fruit Syndrome

Yagami

2002

Food and Agricultural Immunology

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Immediate-type reactions to articles made from natural rubber latex are collectively referred to as latex allergy. Some latex-sensitized patients also experience allergic reactions to various fruits and vegetables. This phenomenon is RESEARCH ON ALLERGENSThere have been recent surprising advancements in immunology, and we expect it to progress even more rapidly and steadily in the future using the genomic information of the human being. By contrast, research on allergenic substances (allergens) is far behind the times. The accumulation of scientific knowledge about the features and modes of action of allergens is

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Calcium–Binding Allergens: From Plants to Man

Cited by 106 publications

References 33 publications

Attenuation of Very Late Antigen-5-Mediated Adhesion of Bone Marrow-Derived Mast Cells to Fibronectin by Peptides with Inverted Hydropathy to EF-Hands

Attenuation of Very Late Antigen-5-Mediated Adhesion of Bone Marrow-Derived Mast Cells to Fibronectin by Peptides with Inverted Hydropathy to EF-Hands

Solution Structure, Dynamics, and Hydrodynamics of the Calcium-bound Cross-reactive Birch Pollen Allergen Bet v 4 Reveal a Canonical Monomeric Two EF-Hand Assembly with a Regulatory Function

Features and Mode of Action of Cross-reactive Plant Allergens Relevant to Latex-fruit Syndrome

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