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TitleStructural basis underlying specific biochemical activities of non-muscle tropomyosin isoforms.
Journal, issue, pagesCell Rep, Vol. 42, Issue 1, Page 111900, Year 2023
Publish dateJan 31, 2023
AuthorsMuniyandi Selvaraj / Shrikant B Kokate / Gabriella Reggiano / Konstantin Kogan / Tommi Kotila / Elena Kremneva / Frank DiMaio / Pekka Lappalainen / Juha T Huiskonen /
PubMed AbstractThe actin cytoskeleton is critical for cell migration, morphogenesis, endocytosis, organelle dynamics, and cytokinesis. To support diverse cellular processes, actin filaments form a variety of ...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.
External linksCell Rep / PubMed:36586407
MethodsEM (helical sym.)
Resolution3.9 - 4.6 Å
Structure data

EMDB-14957, PDB-7ztc:
Non-muscle F-actin decorated with non-muscle tropomyosin 1.6
Method: EM (helical sym.) / Resolution: 3.9 Å

EMDB-14958, PDB-7ztd:
Non-muscle F-actin decorated with non-muscle tropomyosin 3.2
Method: EM (helical sym.) / Resolution: 4.6 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

Source
  • homo sapiens (human)
  • human (human)
KeywordsCYTOSOLIC PROTEIN / actin / tropomyosin / non-muscle / complex

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