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Research Themes Protein-protein interactions

Protein Interaction Networks: Adding Structure to Protein Networks

SBKB [doi:10.1038/sbkb.2012.135]
Technical Highlight - April 2013
Short description: Interactome3D is a tool and resource for annotating protein networks with three-dimensional structure information.

With Interactome3D's homology modeling pipeline, protein networks can be annotated with three-dimensional structural models of protein interactions. 2

Proteins are the workhorses of the cell, carrying out their biological functions in highly coordinated interaction networks. A protein network can be visually represented as a graph, where nodes represent proteins and edges represent the interactions. High-throughput technologies have generated a large amount of information about these networks in a variety of organisms. But those data do not offer insight into the molecular details of protein-protein interactions, which is essential in understanding the function of protein networks.

Aloy and colleagues present Interactome3D, a web tool providing an automated pipeline for modeling protein-protein interactions at atomic resolution in three dimensions.The tool helps highlight the regions of a protein involved in binding to another protein partner. Interactome3D also serves as a resource, offering precalculated models for 12,000 protein-protein interactions in eight model organisms.

The PDB hosts a large and ever-growing number of structures of individual proteins, but structures of protein complexes are still sorely underrepresented. Solving the structures of protein complexes at atomic resolution remains technically challenging, so Interactome3D's modeling pipeline can help pick up where experimental data taper off.

The user-friendly interface of Interactome3D offers a fully automated homology modeling pipeline, so researchers need only input their interaction network of interest for structural annotation. The homology modeling pipeline first collects structural information from the PDB and from high-quality homology models for each protein in the network. Next, experimentally determined structures for each interaction or suitable modeling templates are selected. The templates are then evaluated using a scoring function, and the best of these are used to build the models. Finally, the models are evaluated for completeness and quality.

The authors illustrated the value of Interactome3D by structurally annotating the complement cascade pathway of the innate immune system. They obtained nearly complete structural annotation of this network, allowing them to account for the effects of disease-causing mutations and highlighting interfaces that could be targeted with small molecules to mitigate those effects.

The team has calculated that Interactome3D should be able to provide structural details for an additional 16,000 yet-to-be-discovered interactions, and, with every structure deposited in the PDB, the quality of structural annotation will grow.

Allison Doerr

References

  1. R. Mosca et al. Interactome3D: adding structural details to protein networks.
    Nat. Methods 10, 47-53 (2013). doi:10.1038/nmeth.2289

  2. J. Teyra & P.M. Kim Interpreting protein networks with three-dimensional structures.
    Nat. Methods 10, 43-44 (2013). doi:10.1038/nmeth.2300

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