Structural insights into actin isoforms
- The Ohio State University, United States
- University of Warwick, United Kingdom
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.
Article and author information
Author details
Amandeep Singh Arora
Mohan K Balasubramanian
Krishna Chinthalapudi
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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Structural insights into actin isoforms
eLife 12:e82015.
https://doi.org/10.7554/eLife.82015
