Akademik Veri Yönetim Sistemi
HIBIT2024 (17th International HIBIT Conference), İstanbul, Türkiye, 18 - 20 Aralık 2024, ss.82, (Özet Bildiri)
Defensins are small, cationic peptides with conserved CYS motif which confer stability and functional versatility. They are primarily recognized for their role in innate immune response and essentially all living organisms produce defensin-like peptides(DLPs) to protect themselves against pathogens and external threats. Defensins possess a diverse spectrum of biological activities, such as antimicrobial, antiviral, and antifungal properties. Importantly, DLPs also have the ability to target cancer cells. As a result, DLPs have emerged as a promising class of bioactive molecules for therapeutic applications. Limited structural studies have oÉered insights into the many roles played by DLPs. However, given the pronounced structural conservation of these peptides, a deeper structure-function analysis is needed to elucidate their mechanisms. Therefore, computational comparative structural analysis of diÉerent DLPs may reveal unique structure-activity relationships. In this study, previously uncharacterized fungal DLPs mined from NCBI database. Two candidates from Aspergillus udagawae and Hyaloscypha hepaticicola selected according to their structural and physicochemical properties. These proteins are expressed by our group in the methylotrophic yeast, Pichia pastoris and were shown to undergo pH-dependent oligomerization, which suggests a potential mechanism for their activity regulation(unpublished results). Monomeric DLPs were modelled using AlphaFold and I-TASSER to ensure accuracy and robustness, while oligomeric forms were modelled with AlphaFold Multimer to explore protein-protein interactions. ConSurf server was used to decipher the evolutionary conservation of key DLP motifs. Additionally, a comparative analysis of structural properties such as surface electrostatics&hydrophobicity identified potential residues involved in oligomerization. This study advances our understanding of DLP oligomerization, potentially guiding the development of novel therapeutics.