Abstract
The complex biological processes that control cellular function are mediated by intricate networks of molecular interactions. Accumulating evidence indicates that these interactions are often interdependent, thus acting cooperatively. Cooperative interactions are prevalent in and indispensible for reliable and robust control of cell regulation, as they underlie the conditional decision-making capability of large regulatory complexes. Despite an increased focus on experimental elucidation of the molecular details of cooperative binding events, as evidenced by their growing occurrence in literature, they are currently lacking from the main bioinformatics resources. One of the contributing factors to this deficiency is the lack of a computer-readable standard representation and exchange format for cooperative interaction data. To tackle this shortcoming, we added functionality to the widely used PSI-MI interchange format for molecular interaction data by defining new controlled vocabulary terms that allow annotation of different aspects of cooperativity without making structural changes to the underlying XML schema. As a result, we are able to capture cooperative interaction data in a structured format that is backward compatible with PSI-MI–based data and applications. This will facilitate the storage, exchange and analysis of cooperative interaction data, which in turn will advance experimental research on this fundamental principle in biology.Database URL: http://psi-mi-cooperativeinteractions.embl.de/
Highlights
Cells are subject to ever changing environmental or cell state-specific conditions, and must continuously monitor and integrate a wide variety of external and internal signals to generate appropriate responses
Adjacent interaction sites can mediate multivalent binding [3]. These features allow the interactions of proteins, RNA or DNA to be regulated by the two basic mechanisms underlying cooperative binding: allostery, where the functional properties of a molecule at one site are altered by a perturbation at a distinct site [7, 25], or pre-assembly, where pre-formation of a complex affects interactions of its components through different non-allosteric mechanisms [3, 5, 7]
As this strategy avoids making structural changes to the XML schema, backward compatibility is maintained. To illustrate how such interactions can be captured in the PSI-MI format, data from several publications studying the molecular mechanisms involved in the phosphorylation of substrates, in this case Cell division control protein 6 homolog (Cdc6), by the Cyclin A-Cdk2 complex were collected, and the interdependencies between the different binding events that are involved were annotated in a PSI-MI XML file
Summary
Cells are subject to ever changing environmental or cell state-specific conditions, and must continuously monitor and integrate a wide variety of external and internal signals to generate appropriate responses. These features allow the interactions of proteins, RNA or DNA to be regulated by the two basic mechanisms underlying cooperative binding: allostery, where the functional properties of a molecule at one site are altered by a perturbation at a distinct site [7, 25], or pre-assembly, where pre-formation of a complex affects interactions of its components through different non-allosteric mechanisms [3, 5, 7].
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