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Cited by 22Cellular Mechanics and InteractionsProtein Structure and DynamicsCardiomyopathy and Myosin Studies

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Structural basis underlying specific biochemical activities of non-muscle tropomyosin isoforms

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Selvaraj, Muniyandi, Kokate, Shrikant B., Reggiano, Gabriella, Kogan, Konstantin, Kotila, Tommi, Kremneva, Elena, DiMaio, Frank, Lappalainen, Pekka, Huiskonen, Juha T.·2023·Cell Reports
DOI 10.1016/j.celrep.2022.111900

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Abstract

The actin cytoskeleton is critical for cell migration, morphogenesis, endocytosis, organelle dynamics, and cytokinesis. To support diverse cellular processes, actin filaments form a variety of structures with specific architectures and dynamic properties. Key proteins specifying actin filaments are tropomyosins. Non-muscle cells express several functionally non-redundant tropomyosin isoforms, which differentially control the interactions of other proteins, including myosins and ADF/cofilin, with actin filaments. However, the underlying molecular mechanisms have remained elusive. By determining the cryogenic electron microscopy structures of actin filaments decorated by two functionally distinct non-muscle tropomyosin isoforms, Tpm1.6 and Tpm3.2, we reveal that actin filament conformation remains unaffected upon binding. However, Tpm1.6 and Tpm3.2 follow different paths along the actin filament major groove, providing an explanation for their incapability to co-polymerize on actin filaments. We also elucidate the molecular basis underlying specific roles of Tpm1.6 and Tpm3.2 in myosin II activation and protecting actin filaments from ADF/cofilin-catalyzed severing.

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Metadata

Authors
Selvaraj, M., Kokate, S. B., Reggiano, G., Kogan, K., Kotila, T., Kremneva, E., DiMaio, F., Lappalainen, P., & Huiskonen, J. T.
Affiliations
  • University of Helsinki (FI)
  • University of Washington (US)
Corresponding author
  • Lappalainen, Pekka
  • Huiskonen, Juha T.
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2023-01
Volume
42
Issue
1
Pages
111900
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2022.111900
OpenAlex
W4313379699
Cited by
22
References
1
Citations by year
2026: 4 · 2025: 8 · 2024: 7 · 2023: 3
FWCI
2.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
  • Sigrid Juséliuksen Säätiö (4708344)
  • Helsinki Institute of Life Science, Helsingin Yliopisto
  • Biocenter Finland
  • Academy of Finland (346133)
  • China Scholarship Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
Keywords
tropomyosin isoforms, actin filament structure, ADF/cofilin, actin filament severing, actin cytoskeleton
MeSH terms
Actins, Actin Cytoskeleton, Protein Binding, Tropomyosin, Protein Isoforms, Actin Depolymerizing Factors

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