Structural similarity of genetically interacting proteins

Oranit Dror, Dina Schneidman-Duhovny, Alexandra Shulman-Peleg, Ruth Nussinov, Haim J. Wolfson*, Roded Sharan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: The study of gene mutants and their interactions is fundamental to understanding gene function and backup mechanisms within the cell. The recent availability of large scale genetic interaction networks in yeast and worm allows the investigation of the biological mechanisms underlying these interactions at a global scale. To date, less than 2% of the known genetic interactions in yeast or worm can be accounted for by sequence similarity. Results: Here, we perform a genome-scale structural comparison among protein pairs in the two species. We show that significant fractions of genetic interactions involve structurally similar proteins, spanning 7-10% and 14% of all known interactions in yeast and worm, respectively. We identify several structural features that are predictive of genetic interactions and show their superiority over sequence-based features. Conclusion: Structural similarity is an important property that can explain and predict genetic interactions. According to the available data, the most abundant mechanism for genetic interactions among structurally similar proteins is a common interacting partner shared by two genetically interacting proteins.

Original languageEnglish
Article number69
JournalBMC Systems Biology
StatePublished - 31 Jul 2008


FundersFunder number
Hermann Minkowski-MINERVA Center for Geometry
Israeli Ministry of Science Eshkol Fellowship
National Institutes of HealthNO1-CO-12400, 1UC1AI067231
National Cancer InstituteZIABC010442
National Institute of Allergy and Infectious Diseases
United States-Israel Binational Science Foundation
Israel Science Foundation281/05


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