Open Access Research article

Structural similarity of genetically interacting proteins

Oranit Dror1, Dina Schneidman-Duhovny1, Alexandra Shulman-Peleg1, Ruth Nussinov23, Haim J Wolfson1* and Roded Sharan1

Author Affiliations

1 School of Computer Science, Raymond and Beverly Sackler Faculty of Exact Sciences Tel Aviv University, Tel Aviv, 69978, Israel

2 Basic Research Program, SAIC-Frederick, Inc. Center for Cancer Research Nanobiology Program, NCI, Frederick, MD 21702, USA

3 Department of Human Genetics and Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel

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BMC Systems Biology 2008, 2:69  doi:10.1186/1752-0509-2-69

Published: 31 July 2008



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.


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.


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.