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
Plot of principal eigenvectors of the adjacency matrix (Alevc) for designed protein 1N0R. (a) The principal eigenvectors of the adjacency matrix (Alevc) for designed protein 1N0R is shown. The start and end of each repeat are indicated by dotted and solid lines respectively. (b) The overlap of Alevc profile for the repeat regions is shown. The points in different shapes correspond to the secondary structure elements.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Plot of principal eigenvectors of the adjacency matrix (Alevc) for designed protein 1N0R. (a) The principal eigenvectors of the adjacency matrix (Alevc) for designed protein 1N0R is shown. The start and end of each repeat are indicated by dotted and solid lines respectively. (b) The overlap of Alevc profile for the repeat regions is shown. The points in different shapes correspond to the secondary structure elements.

Mentions: The typical architecture of Ankyrin repeat motif is helix-turn-helix with the two helices anti-parallel and followed by a long variable loop which ends in a beta-turn, shown in Figure 1(a,b) and the eigenvector components of the principal eigenvalue of the adjacency matrix (Alevc) is shown in Figure 1(c). The two peaks marked in Figure 1(c) fall within the helix regions and their large Alevc values are due to dense connections in the compact helical structures. A designed protein 1N0R (chain A) with four ANK repeats is shown in Figure 2(a) and its protein contact network in Figure 2(b). The 3-dimensional topology is well captured by the Alevc profile for each repeat unit as shown in Figure 3(a) for protein 1N0R. Based on secondary structure annotation as provided by STRIDE [42], we observe that both the helices and loop regions exhibit significant variation in their lengths as a result of insertions/deletions and is summarized in Table 1.Figure 3


Identifying tandem Ankyrin repeats in protein structures.

Chakrabarty B, Parekh N - BMC Bioinformatics (2014)

Plot of principal eigenvectors of the adjacency matrix (Alevc) for designed protein 1N0R. (a) The principal eigenvectors of the adjacency matrix (Alevc) for designed protein 1N0R is shown. The start and end of each repeat are indicated by dotted and solid lines respectively. (b) The overlap of Alevc profile for the repeat regions is shown. The points in different shapes correspond to the secondary structure elements.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Plot of principal eigenvectors of the adjacency matrix (Alevc) for designed protein 1N0R. (a) The principal eigenvectors of the adjacency matrix (Alevc) for designed protein 1N0R is shown. The start and end of each repeat are indicated by dotted and solid lines respectively. (b) The overlap of Alevc profile for the repeat regions is shown. The points in different shapes correspond to the secondary structure elements.
Mentions: The typical architecture of Ankyrin repeat motif is helix-turn-helix with the two helices anti-parallel and followed by a long variable loop which ends in a beta-turn, shown in Figure 1(a,b) and the eigenvector components of the principal eigenvalue of the adjacency matrix (Alevc) is shown in Figure 1(c). The two peaks marked in Figure 1(c) fall within the helix regions and their large Alevc values are due to dense connections in the compact helical structures. A designed protein 1N0R (chain A) with four ANK repeats is shown in Figure 2(a) and its protein contact network in Figure 2(b). The 3-dimensional topology is well captured by the Alevc profile for each repeat unit as shown in Figure 3(a) for protein 1N0R. Based on secondary structure annotation as provided by STRIDE [42], we observe that both the helices and loop regions exhibit significant variation in their lengths as a result of insertions/deletions and is summarized in Table 1.Figure 3

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