Primerjava tridimenzionalnih proteinskih struktur alergena breze Bet v 1 in navzkrižno reaktivnih proteinov iz hrane z uporabo bioinformacijskih orodij COMPASS in PDBeFold

Skrt, Ana (avtor), Tavčar, Eva (mentor), Vidak, Marko (komentor)

Alergija je imunsko pogojena preobčutljivost organizma na snovi, ki sicer niso škodljive. Svetovna organizacija za alergije poudarja, da bi morale biti alergijske bolezni prepoznane kot pomemben javnozdravstveni problem. Alergijske reakcije sprožijo alergeni, večinoma proteini, ki povzročijo takojšnjo preobčutljivostno reakcijo, posredovano s protitelesi IgE. Pogost pojav je navzkrižna reaktivnost, pri kateri protitelo, ustvarjeno proti enemu antigenu, prepozna in reagira z drugim, strukturno podobnim antigenom. Kot potencialno navzkrižno reaktivni proteini se običajno prepoznajo tisti, ki si delijo relativno visoko podobnost v primarnem aminokislinskem zaporedju. Vendar poznamo primere proteinov, ki kljub majhni podobnosti v primarnem zaporedju z alergenom navzkrižno reagirajo zaradi podobnosti v tridimenzionalni strukturi. V magistrski nalogi smo želeli pokazati, da je ujemanje tridimenzionalnih struktur znanih alergenov in navzkrižno reaktivnih proteinov iz hrane na splošno večje kot ujemanje njihovih primarnih struktur. Kot tipičen primer znanega alergena smo uporabili alergen Bet v 1 iz cvetnega prahu breze. V literaturi smo najprej poiskali proteine iz hrane, ki eksperimentalno dokazano navzkrižno reagirajo z Bet v 1. Nato smo z bioinformacijskim orodjem COMPASS izvedli primerjavo primarnih struktur treh izoform Bet v 1 s celotno bazo alergenih proteinov COMPARE in v nadaljnjo analizo vključili le navzkrižno reaktivne prehranske proteine. V drugem koraku smo izvedli primerjavo tridimenzionalnih struktur proteinov iz hrane s tremi izoformami Bet v 1, za katere smo našli eksperimentalno določene strukture. Primerjavo smo izvedli z bioinformacijskim orodjem PDBeFold, ki uporablja metodo sekundarnega strukturnega ujemanja. Primerjali smo podobnost proteinov na primarni in terciarni ravni ter ugotovili, da si preiskovani navzkrižno reaktivni proteini med sabo delijo zelo različne stopnje podobnosti v aminokislinskem zaporedju, medtem ko v vseh primerih izkazujejo visoko podobnost v tridimenzionalnih strukturah. Izkazalo se je, da je strukturna podobnost navzkrižno reaktivnih proteinov iz hrane z Bet v 1 v večini primerov večja na terciarni kot na primarni ravni.

• Jezik: Slovenski jezik
• Ključne besede: navzkrižna reaktivnost, cvetni prah, hrana, proteini, bioinformatika
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2024
• PID: 20.500.12556/RUL-162847
• Datum objave v RUL: 28.09.2024

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Comparison of three-dimensional protein structures of birch allergen Bet v 1 and cross-reactive food proteins with the COMPASS and PDBeFold bioinformatics tools

Izvleček

Allergy is immune-related hypersensitivity of the organism to otherwise harmless substances. The World Allergy Organization emphasizes that allergic diseases should be recognized as a significant public health problem. Allergic reactions are triggered by allergens, mostly proteins, which cause an immediate hypersensitivity reaction mediated by IgE antibodies. A common phenomenon is cross-reactivity, in which an antibody formed against one antigen recognizes and reacts with another, structurally similar antigen. Proteins that share a relatively high similarity in primary amino acid sequence are identified as potentially cross-reactive. However, there are examples of proteins that, despite having little similarity in the primary sequence with the allergen, cross-react due to similarity in the three-dimensional structure. In this master's thesis, we want to demonstrate that the similarity between the three-dimensional structures of known allergens and cross-reactive food proteins is generally higher than the similarity of their primary structures. As a typical example of a known allergen, we used the Bet v 1 allergen from birch pollen. We first searched the literature for food proteins that had been experimentally proven to be cross-reactive with Bet v 1. Then, using the COMPASS bioinformatics tool, we compared the primary structures of three Bet v 1 isoforms with the entire database of allergenic proteins COMPARE and included only cross-reactive food proteins in further analysis. In the second step, we performed a comparison of three-dimensional structures of proteins from food with three Bet v 1 isoforms, for which we found experimentally determined structures. The comparison was carried out with the PDBeFold bioinformatics tool, which uses the method of secondary structural matching. We compared the similarity of proteins at the primary and tertiary levels and found that the investigated cross-reactive proteins share very different degrees of similarity in the amino acid sequence, while in all cases they exhibit high similarity in three-dimensional structures. Thus, the structural similarity of cross-reactive proteins from food with Bet v 1 is in most cases higher at the tertiary level than at the primary level.

• Ključne besede: cross-reactivity, pollen, food, proteins, bioinformatics