Circular permutation in proteins
Encyclopedia
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. As a consequence of the circular permutation, the N-terminus of one protein
shows significant sequence similarity to the C-terminus of the other and vice versa. Artificially created permutations have been used for various purposes in protein engineering
and design
. One of the first naturally occurring circular permutations identified was the swaposin family which are circularly permuted versions of saposins.
is gene duplication
of a precursor gene
. 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 structure
s 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 amino and carboxy termini of the protein are being fused and different termini introduced, while keeping the overall arrangement of secondary structure elements essentially unmodified.
to stabilize proteins. They have been show to decrease the proteolytic
susceptibility of recombinant proteins, They have been used to insert domains
into green fluorescent protein
. 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.
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
that changes the order of amino acids in a protein sequence, resulting in a protein structure
Protein structure
Proteins are an important class of biological macromolecules present in all organisms. Proteins are polymers of amino acids. Classified by their physical size, proteins are nanoparticles . Each protein polymer – also known as a polypeptide – consists of a sequence formed from 20 possible L-α-amino...
with different connectivity, but overall similar three dimensional shape. As a consequence of the circular permutation, the N-terminus of one protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
shows significant sequence similarity to the C-terminus of the other and vice versa. Artificially created permutations have been used for various purposes in protein engineering
Protein engineering
Protein engineering is the process of developing useful or valuable proteins. It is a young discipline, with much research taking place into the understanding of protein folding and recognition for protein design principles....
and design
Protein design
Protein design is the design of new protein molecules, either from scratch or by making calculated variations on a known structure. The use of rational design techniques for proteins is a major aspect of protein engineering....
. One of the first naturally occurring circular permutations identified was the swaposin family which are circularly permuted versions of saposins.
Evolution
A model that can explain how circular permutations can occur during evolutionEvolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
is gene duplication
Gene duplication
Gene duplication is any duplication of a region of DNA that contains a gene; it may occur as an error in homologous recombination, a retrotransposition event, or duplication of an entire chromosome.The second copy of the gene is often free from selective pressure — that is, mutations of it have no...
of a precursor gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. If both genes become fused this leads to a tandem protein. The 5' and 3’
Directionality (molecular biology)
Directionality, in molecular biology and biochemistry, is the end-to-end chemical orientation of a single strand of nucleic acid. The chemical convention of naming carbon atoms in the nucleotide sugar-ring numerically gives rise to a 5′-end and a 3′-end...
part of the gene can get lost again for example by insertion of a stop codon
Stop codon
In the genetic code, a stop codon is a nucleotide triplet within messenger RNA that signals a termination of translation. Proteins are based on polypeptides, which are unique sequences of amino acids. Most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide...
.
Many protein structure
Protein structure
Proteins are an important class of biological macromolecules present in all organisms. Proteins are polymers of amino acids. Classified by their physical size, proteins are nanoparticles . Each protein polymer – also known as a polypeptide – consists of a sequence formed from 20 possible L-α-amino...
s 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 amino and carboxy termini of the protein are being fused and different termini introduced, while keeping the overall arrangement of secondary structure elements essentially unmodified.
Role in protein engineering
Artificially constructed circularly permuted proteins are being used in protein engineeringProtein engineering
Protein engineering is the process of developing useful or valuable proteins. It is a young discipline, with much research taking place into the understanding of protein folding and recognition for protein design principles....
to stabilize proteins. They have been show to decrease the proteolytic
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
susceptibility of recombinant proteins, They have been used to insert domains
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
into green fluorescent protein
Green fluorescent protein
The green fluorescent protein is a protein composed of 238 amino acid residues that exhibits bright green fluorescence when exposed to blue light. Although many other marine organisms have similar green fluorescent proteins, GFP traditionally refers to the protein first isolated from the...
. There are several studies that use circular permutations to manipulate protein scaffolds, resulting in improved catalytic activity
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
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.