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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.

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MSA of the repeat regions in protein 3EHQ. (a) predicted by the proposed approach, (b) annotated in the UniProt database, and (c) predicted by ConSole output.
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Fig6: MSA of the repeat regions in protein 3EHQ. (a) predicted by the proposed approach, (b) annotated in the UniProt database, and (c) predicted by ConSole output.

Mentions: We next consider an example of a natural protein, Osteoclast-stimulating factor 1, 3EHQ (chain A), that induces bone resorption. According to the annotation in UniProt, it contains three Ankyrin repeats from 72–168 as shown in the 3-D structure by different colours in Figure 5(a). In Figure 5(b) is shown the Alevc profile plot for 3EHQ, clearly indicating the presence of three repeating units in the region 72–177. There is a good agreement between the predicted start-end boundaries of the three repeat units with the UniProt annotation (see Table 2). However, the prediction of the repeat regions by RADAR and ConSole are not in accordance with the UniProt annotation. The RADAR prediction differs both in terms of the copy number and the repeat boundaries, the first repeat being completely missed. ConSole predicts three copies of the ANK repeats, but the positions of the start-end boundaries of the repeating units are off by about 10 residues for each repeat copy. In Figure 6 is shown the MSA of the repeat regions (a) predicted by our approach, (b) annotated in the UniProt database, and (c) predicted by ConSole. The MSA of the predicted repeat region in Figure 6(a) is in very good agreement with that of the UniProt annotated repeat regions (Figure 6(b)), compared to that of the ConSole predicted region in Figure 6(c). The results for a representative set of 15 ANK repeat proteins is summarized in Table 2 along with the annotation provided in UniProt database, and predictions by sequence and structure based methods, RADAR and ConSole, respectively. By and large we observe a good agreement in the detection of Ankyrin repeats both in copy number as well as repeat boundaries with UniProt annotation and also with ConSole.Figure 5


Identifying tandem Ankyrin repeats in protein structures.

Chakrabarty B, Parekh N - BMC Bioinformatics (2014)

MSA of the repeat regions in protein 3EHQ. (a) predicted by the proposed approach, (b) annotated in the UniProt database, and (c) predicted by ConSole output.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig6: MSA of the repeat regions in protein 3EHQ. (a) predicted by the proposed approach, (b) annotated in the UniProt database, and (c) predicted by ConSole output.
Mentions: We next consider an example of a natural protein, Osteoclast-stimulating factor 1, 3EHQ (chain A), that induces bone resorption. According to the annotation in UniProt, it contains three Ankyrin repeats from 72–168 as shown in the 3-D structure by different colours in Figure 5(a). In Figure 5(b) is shown the Alevc profile plot for 3EHQ, clearly indicating the presence of three repeating units in the region 72–177. There is a good agreement between the predicted start-end boundaries of the three repeat units with the UniProt annotation (see Table 2). However, the prediction of the repeat regions by RADAR and ConSole are not in accordance with the UniProt annotation. The RADAR prediction differs both in terms of the copy number and the repeat boundaries, the first repeat being completely missed. ConSole predicts three copies of the ANK repeats, but the positions of the start-end boundaries of the repeating units are off by about 10 residues for each repeat copy. In Figure 6 is shown the MSA of the repeat regions (a) predicted by our approach, (b) annotated in the UniProt database, and (c) predicted by ConSole. The MSA of the predicted repeat region in Figure 6(a) is in very good agreement with that of the UniProt annotated repeat regions (Figure 6(b)), compared to that of the ConSole predicted region in Figure 6(c). The results for a representative set of 15 ANK repeat proteins is summarized in Table 2 along with the annotation provided in UniProt database, and predictions by sequence and structure based methods, RADAR and ConSole, respectively. By and large we observe a good agreement in the detection of Ankyrin repeats both in copy number as well as repeat boundaries with UniProt annotation and also with ConSole.Figure 5

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