Unraveling the diversity of protein-carbohydrate interfaces: Insights from a multi-scale study.

Protein-carbohydrate interactions play a crucial role in numerous fundamental biological processes. Thus, description and comparison of the carbohydrate binding site (CBS) architecture is of great importance for understanding of the underlying biological mechanisms. However, traditional approaches for carbohydrate-binding protein analysis and annotation rely primarily on the sequence-based methods applied to specific protein classes. The recently released DIONYSUS database aims to fill this gap by providing tools for CBS comparison at different levels: both in terms of protein properties and classification, as well as in terms of atomistic CBS organization. In the current study, we explore DIONYSUS content using a combination of the suggested approaches in order to evaluate the diversity of the currently resolved non-covalent protein-carbohydrate interfaces at different scales. Notably, our analysis reveals evolutionary convergence of CBS in proteins with distinct folds and coming from organisms across different kingdoms of life. Furthermore, we demonstrate that a CBS structure based approach has the potential to facilitate functional annotation for the proteins with missing information in the existing databases. In particular, it provides reliable information for numerous carbohydrate-binding proteins from rapidly evolving organisms, whose analysis is particularly challenging for classical sequence-based methods.