Identifying molecular features that are associated with biological function of intrinsically disordered protein regions

  1. Taraneh Zarin  Is a corresponding author
  2. Bob Strome
  3. Gang Peng
  4. Iva Pritišanac
  5. Julie Deborah Forman-Kay
  6. Alan M Moses  Is a corresponding author
  1. University of Toronto, Canada
  2. 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

  1. Taraneh Zarin

    Department of Cell and Systems Biology, University of Toronto, Toronto, Canada
    For correspondence
    taraneh.zarin@mail.utoronto.ca
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1253-3843
  2. Bob Strome

    Department of Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  3. Gang Peng

    Department of Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  4. Iva Pritišanac

    Program in Molecular Medicine, Hospital for Sick Children, Toronto, Canada
    Competing interests
    No competing interests declared.
  5. Julie Deborah Forman-Kay

    Program in Molecular Medicine, Hospital for Sick Children, Toronto, Canada
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8265-972X
  6. Alan M Moses

    Department of Cell and Systems Biology, University of Toronto, Toronto, Canada
    For correspondence
    alan.moses@utoronto.ca
    Competing interests
    Alan M Moses, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3118-3121

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.

Reviewing Editor

  1. Michael B Eisen, University of California, Berkeley, United States

Publication history

  1. Received: June 23, 2020
  2. Accepted: February 22, 2021
  3. Accepted Manuscript published: February 22, 2021 (version 1)
  4. Version of Record published: March 4, 2021 (version 2)

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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  1. Taraneh Zarin
  2. Bob Strome
  3. Gang Peng
  4. Iva Pritišanac
  5. Julie Deborah Forman-Kay
  6. Alan M Moses
(2021)
Identifying molecular features that are associated with biological function of intrinsically disordered protein regions
eLife 10:e60220.
https://doi.org/10.7554/eLife.60220

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