Accurate contact-based modelling of repeat proteins predicts the structure of new repeats protein families.

Claudio Bassot,Arne Elofsson,Johannes Soeding

doi:10.1371/journal.pcbi.1008798

Claudio Bassot, Arne Elofsson + Show 1 more

Open Access

https://doi.org/10.1371/journal.pcbi.1008798

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Abstract

Repeat proteins are abundant in eukaryotic proteomes. They are involved in many eukaryotic specific functions, including signalling. For many of these proteins, the structure is not known, as they are difficult to crystallise. Today, using direct coupling analysis and deep learning it is often possible to predict a protein's structure. However, the unique sequence features present in repeat proteins have been a challenge to use direct coupling analysis for predicting contacts. Here, we show that deep learning-based methods (trRosetta, DeepMetaPsicov (DMP) and PconsC4) overcomes this problem and can predict intra- and inter-unit contacts in repeat proteins. In a benchmark dataset of 815 repeat proteins, about 90% can be correctly modelled. Further, among 48 PFAM families lacking a protein structure, we produce models of forty-one families with estimated high accuracy.

Highlights

Repeat proteins contain periodic units in the primary sequence that are likely the result of duplication events at the genetic level [1]
General contact prediction analysis in repeat proteins To assess the quality of the contacts predictions among repeat protein classes, we generate a dataset of proteins using the reviewed entries of RepeatsDB [14] and clustered at 40% sequence identity
Using the multiple sequence alignments (MSA) as input for trRosetta, PconsC4, DeepMetaPsicov, and GaussDCA contacts were predicted for each family

Summary

Author summary

Repeat proteins are widespread among organisms and abundant in eukaryotic proteomes. Their primary sequence presents repetition in the amino acid sequences that origin structures with repeated folds/domains. We used contact prediction for predicting the structure of repeats protein directly from their primary sequences. We benchmark the methods on a dataset comprehensive of all the known repeated structures. We evaluate the contact predictions and the obtained models for different classes of repeat proteins. We develop and benchmark a quality assessment (QA) method specific for repeat proteins. We used the prediction pipeline for all PFAM repeat families without resolved structures and found that forty-one of them could be modelled with high accuracy

Introduction

Results and discussion

Conclusion

Materials and methods