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

Authors :
Muniyandi Selvaraj
Shrikant B. Kokate
Gabriella Reggiano
Konstantin Kogan
Tommi Kotila
Elena Kremneva
Frank DiMaio
Pekka Lappalainen
Juha T. Huiskonen
Institute of Biotechnology
Pekka Lappalainen / Principal Investigator
Publication Year :
2022
Publisher :
Cold Spring Harbor Laboratory, 2022.

Abstract

SUMMARYThe 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 major groove of the actin filament, providing an explanation for their incapability to co-polymerize on actin filaments. The structures and biochemical work 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-catalysed severing.

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....d6808c094662c1ce49a5dcf07052712c
Full Text :
https://doi.org/10.1101/2022.05.12.491677