Influence of alternative splicing events to secondary structure of proteins

Alternative splicing (AS) is an import biological process, which enables a high variability in the proteom of eukaryotes. Up to 95 % of all multi exon genes in human undergo AS. Errors during the splicing can cause diseases, e.g. cancer and neuronal disorders.In this work we present a method to collect information of alternative spliced proteins from several sources, which are combined to one single entry. Seeing that many experimentally determined structure data are freely available online, an automatic analysis of the effects of alternative splicing on the protein structure becomes possible.

Therefore we implemented a pipeline which process AS data based on SwissProt, PDB and InterPro. We identified possible changes of the protein fold on secondary structure level. We used DSSP to assign secondary structure elements (SSEs), which are then classified according the splicing effects. To connect all data sources, we developed an adapted alignment, which contains three sequence types: Isoform / PDB / SSE. Moreover, we implemented a visualization of the results.

Parsing 2,289 proteins in SwissProt we identified 758 proteins, which contain at least one SSE which is alternative spliced. Ten proteins with PDB data of both variants of a single splicing event were found and a direct comparison of the tertiary structure is possible. We provide a statistical overview and explain a case study in detail.

The pipeline we implemented can be used for large-scale analysis of AS data.