The scientific results of the Institute of Biophysics together with the University of Montpellier are published in the journal with a high impact factor

Alternative splicing is an important means of generating the protein diversity necessary for cellular functions. Hence, there is a growing interest in assessing the structural and functional impact of alternative protein isoforms. Typically, experimental studies are used to determine the structures of the canonical proteins ignoring the other isoforms. Therefore, there is still a large gap between abundant sequence information and meager structural data on these isoforms. During the last decade, significant progress has been achieved in the development of bioinformatics tools for structural and functional annotations of proteins. Moreover, the appearance of the AlphaFold program opened up the possibility to model a large number of high-confidence structures of the isoforms. In this study, using state-of-the-art tools, we performed in silico analysis of 58 eukaryotic proteomes. The evaluated structural states included structured domains, intrinsically disordered regions, aggregation-prone regions, and tandem repeats. Among other things, we found that the isoforms have fewer signal peptides, transmembrane regions, or tandem repeat regions in comparison with their canonical counterparts. This could change protein function and/or cellular localization. The AlphaFold modeling demonstrated that frequently isoforms, having differences with the canonical sequences, still can fold in similar structures though with significant structural rearrangements which can lead to changes of their functions. Based on the modeling, we suggested classification of the structural differences between canonical proteins and isoforms. Altogether, we can conclude that a majority of isoforms, similarly to the canonical proteins are under selective pressure for the functional roles.

Recently, the results of these studies conducted by a doctoral student of ANAS and the University of Montpellier of France Zarifa Osmanli, and her colleagues (including Turkan Samedova, a doctoral student of ANAS and the University of Montpellier, and the head of the laboratory “Integrative Biology” of the Institute of Biophysics, corresponding member of ANAS Ilham Shahmuradov) were published in the journal “Biomolecules” with a high impact factor of 4.6.

03 November 2022

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