1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics

Structural insights into actin isoforms

  1. Amandeep Singh Arora
  2. Hsiang-Ling Huang
  3. Ramanpreet Singh
  4. Yoshie Narui
  5. Andrejus Suchenko
  6. Tomoyuki Hatano
  7. Sarah M Heissler
  8. Mohan K Balasubramanian
  9. Krishna Chinthalapudi  Is a corresponding author
  1. The Ohio State University, United States
  2. University of Warwick, United Kingdom
https://doi.org/10.7554/eLife.82015
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  1. Amandeep Singh Arora
  2. Hsiang-Ling Huang
  3. Ramanpreet Singh
  4. Yoshie Narui
  5. Andrejus Suchenko
  6. Tomoyuki Hatano
  7. Sarah M Heissler
  8. Mohan K Balasubramanian
  9. Krishna Chinthalapudi
(2023)
Structural insights into actin isoforms
eLife 12:e82015.
https://doi.org/10.7554/eLife.82015
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Abstract

Actin isoforms organize into distinct networks that are essential for the normal function of eukaryotic cells. Despite a high level of sequence and structure conservation, subtle differences in their design principles determine the interaction with myosin motors and actin-binding proteins (ABPs). Therefore, identifying how the structure of actin isoforms relates to function is important for our understanding of normal cytoskeletal physiology. Here, we report the high-resolution structures of filamentous skeletal muscle a-actin (3.37Å), cardiac muscle a-actin (3.07Å), ß-actin (2.99Å), and g-actin (3.38Å) in the Mg2+·ADP state with their native PTMs. The structures revealed isoform-specific conformations of the N-terminus that shift closer to the filament surface upon myosin binding, thereby establishing isoform-specific interfaces. Collectively, the structures of single-isotype, post-translationally modified bare skeletal muscle a-actin, cardiac muscle a-actin, ß-actin, and g-actin reveal general principles, similarities, and differences between isoforms. They complement the repertoire of known actin structures and allow for a comprehensive understanding of in vitro and in vivo functions of actin isoforms.

Data availability

All the structures and electron density maps generated have been deposited in the Protein Data Bank (PDB) and Electron Microscopy Data Bank (EMDB). The PDB and EMDB entries are 8DMX and EMD-27548; 8DMY and EMD-27549; 8DNH and EMD-27572; 8DNF and EMD-27565.

The following data sets were generated

Article and author information

Author details

  1. Amandeep Singh Arora

    Department of Physiology and Cell Biology, The Ohio State University, Columbus, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1045-1967

  2. Hsiang-Ling Huang

    Department of Physiology and Cell Biology, The Ohio State University, Columbus, United States
    Competing interests
    No competing interests declared.

  3. Ramanpreet Singh

    Department of Physiology and Cell Biology, The Ohio State University, Columbus, United States
    Competing interests
    No competing interests declared.

  4. Yoshie Narui

    Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, United States
    Competing interests
    No competing interests declared.

  5. Andrejus Suchenko

    Centre for Mechanochemical Cell Biology, University of Warwick, Coventry, United Kingdom
    Competing interests
    No competing interests declared.

  6. Tomoyuki Hatano

    Division of Biomedical Sciences, University of Warwick, Coventry, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9092-3989

  7. Sarah M Heissler

    Department of Physiology and Cell Biology, The Ohio State University, Columbus, United States
    Competing interests
    No competing interests declared.

  8. Mohan K Balasubramanian

    Division of Biomedical Sciences, University of Warwick, Coventry, United Kingdom
    Competing interests
    Mohan K Balasubramanian, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1292-8602

  9. Krishna Chinthalapudi

    Department of Physiology and Cell Biology, The Ohio State University, Columbus, United States
    For correspondence
    krishna.chinthalapudi@osumc.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3669-561X

Funding

National Institutes of Health (R01GM143539)

  • Krishna Chinthalapudi

National Institutes of Health (K22HL131869)

  • Sarah M Heissler

Wellcome Trust (203276/Z/16/Z)

  • Mohan K Balasubramanian

European Research Council (ERC-2014-ADG No. 671083)

  • Mohan K Balasubramanian

Biotechnology and Biological Sciences Research Council (BB/S003789/1)

  • Mohan K Balasubramanian

National Institutes of Health (R01GM143414)

  • Sarah M Heissler

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2023, Arora 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. Amandeep Singh Arora
  2. Hsiang-Ling Huang
  3. Ramanpreet Singh
  4. Yoshie Narui
  5. Andrejus Suchenko
  6. Tomoyuki Hatano
  7. Sarah M Heissler
  8. Mohan K Balasubramanian
  9. Krishna Chinthalapudi
(2023)
Structural insights into actin isoforms
eLife 12:e82015.
https://doi.org/10.7554/eLife.82015

Share this article

https://doi.org/10.7554/eLife.82015

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