Isoforms of cancer-related proteins tend to destabilize the structure

Osmanli, Zarifa; Aliyeva, Aysel; Shahmuradov, Ilham

Isoforms of cancer-related proteins tend to destabilize the structure

2023

Osmanli, Zarifa | Aliyeva, Aysel | Shahmuradov, Ilham

Protein isoforms provide protein diversity through various biological mechanisms such as alternative splicing, alternative promoter usage and other mechanisms. Isoforms functions can differ depending on several factors, including their amino acid sequence and structure. Meanwhile, cancer-related protein isoforms have notable importance due to their association with the disease. Previous studies indicate that tumor suppressor protein p53 isoforms can either facilitate or inhibit tumor growth, depending on its isoform and the cellular context. However, earlier studies have mainly focused on investigating the structures of canonical proteins of cancer-related proteins, with relatively less attention given to the structural analysis of their isoforms. Determining the structure of isoforms of cancer-related proteins can be crucial for understanding the mechanisms of disease association. Changes in structure may affect the function of isoforms. Experimental studies can be expensive and time-consuming, frequently requiring significant resources to obtain accurate results. Nonetheless, recent advancements in structural biology, such as the AlphaFold tool, have provided a door of opportunity to study protein sequences deeply. Thanks to this tool, we can model highly accurate protein structures without the need for comprehensive laboratory research, allowing for more efficient and cost-effective research. Therefore, in our study, we implemented a comparative analysis of the canonical cancer-related proteins and their isoform structures made with AlphaFold to determine structural differences. Our analysis revealed that most of the isoforms of cancer-related proteins are more disordered than general protein isoforms.

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