Limits...
Identifying tandem Ankyrin repeats in protein structures.

Chakrabarty B, Parekh N - BMC Bioinformatics (2014)

Bottom Line: Topology of repeating unit and its frequency of occurrence are associated to a wide range of structural and functional roles in diverse proteins, and defects in repeat proteins have been associated with a number of diseases.It is evaluated on a set of 370 proteins comprising 125 known Ankyrin proteins and remaining non-solenoid proteins and the prediction compared with UniProt annotation, sequence-based approach, RADAR, and structure-based approach, ConSole.This method is especially useful in correctly identifying new members of a repeat family.

View Article: PubMed Central - PubMed

Affiliation: Centre for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Hyderabad, India. broto.chakrabarty@research.iiit.ac.in.

ABSTRACT

Background: Tandem repetition of structural motifs in proteins is frequently observed across all forms of life. Topology of repeating unit and its frequency of occurrence are associated to a wide range of structural and functional roles in diverse proteins, and defects in repeat proteins have been associated with a number of diseases. It is thus desirable to accurately identify specific repeat type and its copy number. Weak evolutionary constraints on repeat units and insertions/deletions between them make their identification difficult at the sequence level and structure based approaches are desired. The proposed graph spectral approach is based on protein structure represented as a graph for detecting one of the most frequently observed structural repeats, Ankyrin repeat.

Results: It has been shown in a large number of studies that 3-dimensional topology of a protein structure is well captured by a graph, making it possible to analyze a complex protein structure as a mathematical entity. In this study we show that eigen spectra profile of a protein structure graph exhibits a unique repetitive profile for contiguous repeating units enabling the detection of the repeat region and the repeat type. The proposed approach uses a non-redundant set of 58 Ankyrin proteins to define rules for the detection of Ankyrin repeat motifs. It is evaluated on a set of 370 proteins comprising 125 known Ankyrin proteins and remaining non-solenoid proteins and the prediction compared with UniProt annotation, sequence-based approach, RADAR, and structure-based approach, ConSole. To show the efficacy of the approach, we analyzed the complete PDB structural database and identified 641 previously unrecognized Ankyrin repeat proteins. We observe a unique eigen spectra profile for different repeat types and show that the method can be easily extended to detect other repeat types. It is implemented as a web server, AnkPred. It is freely available at 'bioinf.iiit.ac.in/AnkPred'.

Conclusions: AnkPred provides an elegant and computationally efficient graph-based approach for detecting Ankyrin structural repeats in proteins. By analyzing the eigen spectra of the protein structure graph and secondary structure information, characteristic features of a known repeat family are identified. This method is especially useful in correctly identifying new members of a repeat family.

Show MeSH
Ankyrin repeat motif. (a) The second copy of the ANK structural motif in designed protein 1N0R. (b) Schematic diagram showing the secondary structure arrangement in the ANK motif. (c) The principal eigenvector of adjacency matrix plotted for the ANK motif in (a).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4307672&req=5

Fig1: Ankyrin repeat motif. (a) The second copy of the ANK structural motif in designed protein 1N0R. (b) Schematic diagram showing the secondary structure arrangement in the ANK motif. (c) The principal eigenvector of adjacency matrix plotted for the ANK motif in (a).

Mentions: The Ankyrin repeat (ANK) is one of the most frequently observed structural motifs in proteins, especially in eukaryotes. It was first discovered in signalling proteins in yeast cell cycle regulator Cdc10 containing 24 copies of this repeat. In general, 4 to 6 copies of the repeat stack onto each other to form an elongated structure with a continuous hydrophobic core and a large solvent-accessible surface [26]. The protein-protein interaction module is involved in a diverse set of cellular functions, such as transcriptional initiators, cell-cycle regulators, cytoskeletal, ion transporters and signal transducers, and consequently, defects in Ankyrin repeat proteins have been associated with a number of human diseases [27]. For example, mutation in the ANK1 gene producing the erythrocyte ankyrin protein may lead to hereditary spherocytosis [28]. Each repeat typically consists of 30–34 amino acid residues comprising two anti-parallel α-helices and a long loop ending in a β-hairpin (shown in Figure 1(a)) and schematically in Figure 1(b), forming a scaffold for specific, high-affinity molecular interactions. In contrast to many other protein-protein binding motifs, it has been observed that the Ankyrin repeat motif is better characterized by its tertiary structure rather than by a specific function, because of the pronounced sequence variation in the individual repeats and in the copy number variation across various protein families.Figure 1


Identifying tandem Ankyrin repeats in protein structures.

Chakrabarty B, Parekh N - BMC Bioinformatics (2014)

Ankyrin repeat motif. (a) The second copy of the ANK structural motif in designed protein 1N0R. (b) Schematic diagram showing the secondary structure arrangement in the ANK motif. (c) The principal eigenvector of adjacency matrix plotted for the ANK motif in (a).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4307672&req=5

Fig1: Ankyrin repeat motif. (a) The second copy of the ANK structural motif in designed protein 1N0R. (b) Schematic diagram showing the secondary structure arrangement in the ANK motif. (c) The principal eigenvector of adjacency matrix plotted for the ANK motif in (a).
Mentions: The Ankyrin repeat (ANK) is one of the most frequently observed structural motifs in proteins, especially in eukaryotes. It was first discovered in signalling proteins in yeast cell cycle regulator Cdc10 containing 24 copies of this repeat. In general, 4 to 6 copies of the repeat stack onto each other to form an elongated structure with a continuous hydrophobic core and a large solvent-accessible surface [26]. The protein-protein interaction module is involved in a diverse set of cellular functions, such as transcriptional initiators, cell-cycle regulators, cytoskeletal, ion transporters and signal transducers, and consequently, defects in Ankyrin repeat proteins have been associated with a number of human diseases [27]. For example, mutation in the ANK1 gene producing the erythrocyte ankyrin protein may lead to hereditary spherocytosis [28]. Each repeat typically consists of 30–34 amino acid residues comprising two anti-parallel α-helices and a long loop ending in a β-hairpin (shown in Figure 1(a)) and schematically in Figure 1(b), forming a scaffold for specific, high-affinity molecular interactions. In contrast to many other protein-protein binding motifs, it has been observed that the Ankyrin repeat motif is better characterized by its tertiary structure rather than by a specific function, because of the pronounced sequence variation in the individual repeats and in the copy number variation across various protein families.Figure 1

Bottom Line: Topology of repeating unit and its frequency of occurrence are associated to a wide range of structural and functional roles in diverse proteins, and defects in repeat proteins have been associated with a number of diseases.It is evaluated on a set of 370 proteins comprising 125 known Ankyrin proteins and remaining non-solenoid proteins and the prediction compared with UniProt annotation, sequence-based approach, RADAR, and structure-based approach, ConSole.This method is especially useful in correctly identifying new members of a repeat family.

View Article: PubMed Central - PubMed

Affiliation: Centre for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Hyderabad, India. broto.chakrabarty@research.iiit.ac.in.

ABSTRACT

Background: Tandem repetition of structural motifs in proteins is frequently observed across all forms of life. Topology of repeating unit and its frequency of occurrence are associated to a wide range of structural and functional roles in diverse proteins, and defects in repeat proteins have been associated with a number of diseases. It is thus desirable to accurately identify specific repeat type and its copy number. Weak evolutionary constraints on repeat units and insertions/deletions between them make their identification difficult at the sequence level and structure based approaches are desired. The proposed graph spectral approach is based on protein structure represented as a graph for detecting one of the most frequently observed structural repeats, Ankyrin repeat.

Results: It has been shown in a large number of studies that 3-dimensional topology of a protein structure is well captured by a graph, making it possible to analyze a complex protein structure as a mathematical entity. In this study we show that eigen spectra profile of a protein structure graph exhibits a unique repetitive profile for contiguous repeating units enabling the detection of the repeat region and the repeat type. The proposed approach uses a non-redundant set of 58 Ankyrin proteins to define rules for the detection of Ankyrin repeat motifs. It is evaluated on a set of 370 proteins comprising 125 known Ankyrin proteins and remaining non-solenoid proteins and the prediction compared with UniProt annotation, sequence-based approach, RADAR, and structure-based approach, ConSole. To show the efficacy of the approach, we analyzed the complete PDB structural database and identified 641 previously unrecognized Ankyrin repeat proteins. We observe a unique eigen spectra profile for different repeat types and show that the method can be easily extended to detect other repeat types. It is implemented as a web server, AnkPred. It is freely available at 'bioinf.iiit.ac.in/AnkPred'.

Conclusions: AnkPred provides an elegant and computationally efficient graph-based approach for detecting Ankyrin structural repeats in proteins. By analyzing the eigen spectra of the protein structure graph and secondary structure information, characteristic features of a known repeat family are identified. This method is especially useful in correctly identifying new members of a repeat family.

Show MeSH