Projects per year
Abstract
Ankyrin protein repeats bind to a wide range of substrates and are one of the most common protein motifs in nature. Here, we collate a high-quality alignment of 7,407 ankyrin repeats and examine for the first time, the distribution of human population variants from large-scale sequencing of healthy individuals across this family. Population variants are not randomly distributed across the genome but are constrained by gene essentiality and function. Accordingly, we interpret the population variants in context with evolutionary constraint and structural features including secondary structure, accessibility and protein-protein interactions across 383 three-dimensional structures of ankyrin repeats. We find five positions that are highly conserved across homologs and also depleted in missense variants within the human population. These positions are significantly enriched in intra-domain contacts and so likely to be key for repeat packing. In contrast, a group of evolutionarily divergent positions are found to be depleted in missense variants in human but significantly enriched in protein-protein interactions. Our analysis also suggests the domain has three, not two surfaces, each with different patterns of enrichment in protein-substrate interactions and missense variants. Our findings will be of interest to those studying or engineering ankyrin-repeat containing proteins as well as those interpreting the significance of disease variants.
Original language | English |
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Publisher | BioRxiv |
Number of pages | 26 |
DOIs | |
Publication status | Published - 30 May 2021 |
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Dive into the research topics of 'Ankyrin repeats in context with human population variation'. Together they form a unique fingerprint.Projects
- 5 Finished
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The Dundee Resource for Sequence Analysis and Structure Prediction. RELATED TO 36262A, B, C AND D
Barton, G. (Investigator)
Biotechnology and Biological Sciences Research Council
1/09/18 → 31/08/24
Project: Research
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The Jalview Resource for Sequence Analysis and Annotation (Bioinformatics and Biomedical Resource Fund)
Barton, G. (Investigator) & Procter, J. (Investigator)
Biotechnology and Biological Sciences Research Council
1/10/14 → 30/09/19
Project: Research
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Extending The Jalview Resource for Biological Sequence Alignment and Analysis (Biomedical Resource application)
Barton, G. (Investigator)
1/09/14 → 28/02/21
Project: Research
Research output
- 1 Article
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Ankyrin repeats in context with human population variation
Utgés,, J. S., Tsenkov, M. I., Dietrich, N. J. M., MacGowan, S. A. & Barton, G. J. (Lead / Corresponding author), Aug 2021, In: PLoS Computational Biology. 17, 8, 26 p., e1009335.Research output: Contribution to journal › Article › peer-review
Open AccessFile7 Citations (Scopus)122 Downloads (Pure)