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Interactome3D: adding structural details to protein networks

Abstract

Network-centered approaches are increasingly used to understand the fundamentals of biology. However, the molecular details contained in the interaction networks, often necessary to understand cellular processes, are very limited, and the experimental difficulties surrounding the determination of protein complex structures make computational modeling techniques paramount. Here we present Interactome3D, a resource for the structural annotation and modeling of protein-protein interactions. Through the integration of interaction data from the main pathway repositories, we provide structural details at atomic resolution for over 12,000 protein-protein interactions in eight model organisms. Unlike static databases, Interactome3D also allows biologists to upload newly discovered interactions and pathways in any species, select the best combination of structural templates and build three-dimensional models in a fully automated manner. Finally, we illustrate the value of Interactome3D through the structural annotation of the complement cascade pathway, rationalizing a potential common mechanism of action suggested for several disease-causing mutations.

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Figure 1: The Interactome3D pipeline.
Figure 2: Structural coverage of proteins and interactions for eight organisms.
Figure 3: Benchmarking of the homology models of interactions generated by Interactome3D.
Figure 4: Structural annotation of the complement cascade.
Figure 5: Mapping disease mutations in the context of the structural interactome.

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Protein Data Bank

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Protein Data Bank

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Acknowledgements

This work was partially supported by the Spanish Ministerio de Ciencia e Innovación (BIO2010-22073) and the European Commission under FP7 Grant Agreement 223101 (AntiPathoGN).

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Contributions

R.M. conceived and designed the work, wrote the manuscript, developed the pipeline, analyzed the data and implemented the Interactome3D web resource. A.C. compiled the integrated interaction database used by Interactome3D and implemented the Interactome3D web resource. P.A. conceived the work and wrote the manuscript.

Corresponding author

Correspondence to Patrick Aloy.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figs. 1–3, Supplementary Tables 1, 2 and 4 (PDF 630 kb)

Supplementary Table 3

Structures used for the structural annotation of the Complement Cascade pathway (XLSX 30 kb)

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Mosca, R., Céol, A. & Aloy, P. Interactome3D: adding structural details to protein networks. Nat Methods 10, 47–53 (2013). https://doi.org/10.1038/nmeth.2289

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