Circular permutation in proteins
 | This article provides insufficient context for those unfamiliar with the subject. (May 2011) |
Circular Permutation in Proteins
Circular permutation is a process during evolution that changes the order of amino acids in a protein sequence, resulting in a protein structure with different connectivity, but overall similar three dimensional shape. Artificially created permutations have been used for various purposes in protein engineering and design.
Evolution
A model that can explain how circular permutations can occur during evolution is gene duplication of a precursor gene. [1] If both genes become fused this leads to a tandem protein. The 5’ and 3’ part of the gene can get lost again for example by insertion of a stop codon. Many protein structures are observed to have their N- and C-termini in close proximity in space. This characteristic contributes that such permutation events can get tolerated. The N- and C-termini of the protein are fused and different N- and C- termini are being introduced, while keeping the overall arrangements of secondary structure elements essentially unmodified.
The Role of circular permutation in protein engineering
Artificially constructed circularly permuted proteins are being used in protein engineering to stabilize proteins. They have been show to decrease the proteolytic susceptibility of recombinant proteins [2], They have been used used to insert domains into green fluorescent protein [3]. There are several studies that use circular permutations to manipulate protein scaffolds, resulting in improved catalytic activity and altered substrate or ligand binding affinity. Circular permutations have been also used to enable the design of novel biocatalysts and biosensors. For a review on this see [4].
Further reading
- David Goodsell (2010) Concanavalin A and Circular Permutation RCSB PDB Molecule of the Month [1]
References
- ^ Jeltsch A (1999). "Circular permutations in the molecular evolution of DNA methyltransferases". J. Mol. Evol. 49 (1): 161–164. PMID 10368444.
- ^ Whitehead; et al. (2009). "Tying up the loose ends: circular permutation decreases the proteolytic susceptibility of recombinant proteins". Prot Eng. Design. 22 (10): 607–513. PMID 19622546.
{{cite journal}}: Explicit use of et al. in:|author=(help) - ^ Baird GS, Zacharias DA, Tsien RY. (1999). "Circular permutation and receptor insertion within green fluorescent proteins". PNAS. 96 (20): 11241-11246. PMID 10500161.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Yu and Lutz (2011). "Circular permutation: a different way to engineer enzyme structure and function". Trends Biotechnol. 29 (1): 18–25. PMID 21087800.