Identifying molecular features that are associated with biological function of intrinsically disordered protein regions
- University of Toronto, Canada
- Hospital for Sick Children, Canada
Abstract
In previous work, we showed that intrinsically disordered regions (IDRs) of proteins contain sequence-distributed molecular features that are conserved over evolution, despite little sequence similarity that can be detected in alignments (Zarin et al. 2019). Here, we aim to use these molecular features to predict specific biological functions for individual IDRs and identify the molecular features within them that are associated with these functions. We find that the predictable functions are diverse. Examining the associated molecular features, we note some that are consistent with previous reports, and identify others that were previously unknown. We experimentally confirm that elevated isoelectric point and hydrophobicity, features that are positively associated with mitochondrial localization, are necessary for mitochondrial targeting function. Remarkably, increasing isoelectric point in a synthetic IDR restores weak mitochondrial targeting. We believe feature analysis represents a new systematic approach to understand how biological functions of IDRs are specified by their protein sequences.
Data availability
All data generated or analysed during this study are included in the manuscript, supporting files and the accompanying website.
Article and author information
Author details
Julie Deborah Forman-Kay
Funding
Canadian Institutes of Health Research (PJT-148532)
- Julie Deborah Forman-Kay
- Alan M Moses
Canadian Institutes of Health Research (FDN-148375)
- Julie Deborah Forman-Kay
NSERC
- Taraneh Zarin
- Alan M Moses
Canadian Foundation for Innovation
- Alan M Moses
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Zarin et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Identifying molecular features that are associated with biological function of intrinsically disordered protein regions
eLife 10:e60220.
https://doi.org/10.7554/eLife.60220
