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Naturally occurring circular permutations in proteins
1Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel.
Protein Engineering
|October 2, 2001
Summary
Researchers identified 25 protein pairs with circular permutations using a novel screening algorithm. This finding suggests circular permutations in proteins are rare and likely arise from functional unit fusion, not local genetic manipulation.
Area of Science:
- Bioinformatics
- Structural Biology
- Computational Biology
Background:
- Circular permutation defines a specific relationship between protein sequences where N- and C-terminal regions are swapped.
- Detecting such relationships is crucial for understanding protein evolution and function.
Purpose of the Study:
- To develop and apply a computational method for identifying circularly permuted protein pairs.
- To assess the prevalence of circular permutation in protein databases.
Main Methods:
- A fast screening algorithm, a variation of dynamic programming string matching with sequence doubling, was developed.
- Candidate pairs were validated using exhaustive string matching and manual inspection with dotplots.
- Searches were conducted in the Swissprot and Pfam databases.
Main Results:
- Twenty-five independent protein pairs related by circular permutation were identified in Swissprot.
- These pairs were categorized based on functional similarity.
- A systematic search in Pfam yielded only seven additional candidates, none matching the initial definition.
Conclusions:
- The low number of identified cases suggests that mechanisms for inducing local genetic manipulation leading to circular permutation are unlikely.
- Observed instances of circular permutation appear to predominantly result from the fusion of functional protein units.