An in silico approach to the analysis of CTLA-4 and CD28 molecules

CD28 ve CTLA-4, T hücreleri üzerinde eksprese olan önemli ko-stimilatör moleküllerdir ve antijen uyarımı ile T hücre aktivasyonunu düzenlerler. Bu çalışmanın amacı; omurgalı türlerin ilgili moleküllerinin insan CTLA-4 ve CD28 moleküllerine homolog protein dizilerini, promoter dizileri üzerinde genel transkripsiyon faktörlerinin bağlanma yerlerini ve farklı türlerdeki CTLA-4 ve CD28 proteinlerinin IGv domeynlerinin filogenetik ilişkileri gibi bu gen ve ürünlerinin özelliklerini biyoinformatik araçlarla araştırmaktır. Sonuçlarımız, hem CTLA-4 ve hem de CD28 moleküllerinin araştırılan tüm organizmalar arasında orta derecede korunduklarını gösterdi. Çalışmamız insanın hem CD28 hem de CTLA-4 IGv domeynlerinin; Maçaca nemestrina, Cercocebus torquatus atys, Maçaca mulatta ve Papio cynocephalus anubis'in IGv domeynlerine evrimsel olarak en yakın olduğunu göstermiştir. Buna karşın, Gallus gallus'un CD28 ve Mus musculus ile Rattus norvegicus'un CTLA-4 IGv domeynleri ise sırasıyla insanlarınkine en uzaktır. Karşılaştırmalı promoter taraması, hem CTLA-4 ve hem de CD28 genlerinin evrimsel olarak çalışılan bütün türlerde korunmuş bazı transkripsiyon faktörlerinin bağlanma bölgelerine sahip olduklarını göstermiştir.

CTLA-4 ve CD28 moleküllerinin analizine in siliko bir yaklaşım

The CD28 and CTLA-4 are important co-stimulatory molecules expressed on T cells and regulate T cell activation through antigen stimulation. This study aimed to investigate some properties of these genes and its products; such as the homologous protein sequences to human CTLA-4 and CD28 molecules, the common transcription factor binding sites on their promoters, and phylogenetic relationships of their Immunoglobulin V-Type (IGv) domains using bioinformatical approaches. Our results revealed that both CTLA-4 and CD28 molecules are moderately conserved among all organisms investigated. The IGv domains of human CTLA-4 and CD28 are closest to those of Maçaca nemestrina, Cercocebus torquatus atys, Maçaca mulatta and Papio cynocephalus anubis. In contrast, the IGv domain of CD28 of Gallus gallus and that of CTLA-4 of Mus musculus and Rattus norvegicus is most apart from those of human, respectively. The comparative screening of the promoters revealed that both CTLA-4 and CD28 genes have some conserved transcription factor binding sites.

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