ConSole: using modularity of contact maps to locate solenoid domains in protein structures.

Thomas Hrabe,Adam Godzik

doi:10.1186/1471-2105-15-119

Thomas Hrabe, Adam Godzik

Open Access

https://doi.org/10.1186/1471-2105-15-119

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Abstract

BackgroundPeriodic proteins, characterized by the presence of multiple repeats of short motifs, form an interesting and seldom-studied group. Due to often extreme divergence in sequence, detection and analysis of such motifs is performed more reliably on the structural level. Yet, few algorithms have been developed for the detection and analysis of structures of periodic proteins.ResultsConSole recognizes modularity in protein contact maps, allowing for precise identification of repeats in solenoid protein structures, an important subgroup of periodic proteins. Tests on benchmarks show that ConSole has higher recognition accuracy as compared to Raphael, the only other publicly available solenoid structure detection tool. As a next step of ConSole analysis, we show how detection of solenoid repeats in structures can be used to improve sequence recognition of these motifs and to detect subtle irregularities of repeat lengths in three solenoid protein families.ConclusionsThe ConSole algorithm provides a fast and accurate tool to recognize solenoid protein structures as a whole and to identify individual solenoid repeat units from a structure. ConSole is available as a web-based, interactive server and is available for download at http://console.sanfordburnham.org.

Highlights

Periodic proteins, characterized by the presence of multiple repeats of short motifs, form an interesting and seldom-studied group
Other examples include Ankyrin repeats involved in various protein–protein interactions and Armadillo repeats that, together with other homologous classes, such as HEAT repeats, form helical solenoids and are found in proteins involved in cell adhesion [3,4]
The original annotators postulate that an error tolerance of up to 5 residues is acceptable for structural solenoid detectors [6], so the accuracy of our method is well within the tolerance level

Summary

Introduction

Periodic proteins, characterized by the presence of multiple repeats of short motifs, form an interesting and seldom-studied group. Due to often extreme divergence in sequence, detection and analysis of such motifs is performed more reliably on the structural level. Few algorithms have been developed for the detection and analysis of structures of periodic proteins. A well-known example of solenoid proteins are Leucine Rich Repeats (LRRs) present in the innate immunity or receptors (NLR or TLR, respectively) and in thousands of other proteins with various other functions and extremely variable consensus sequences [2]. Accumulated mutations, deletions, and insertions lead to increasing divergence between individual repeats. For many proteins, this divergence can be quite extreme with almost no sequence similarity between individual copies of the ancestral motif [5]. Automated detection of subtle motif variations from sequence is often impossible

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