Tropomyosin position on F-Actin revealed by EM reconstruction and computational chemistry
Electron microscopy and fiber diffraction studies of reconstituted F-actin-tropomyosin filaments reveal the azimuthal position of end-to-end linked tropomyosin molecules on the surface of actin. However, the longitudinal z-position of tropomyosin along F-actin is still uncertain. Without this inform...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
February 2011
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| In: |
Biophysical journal
Year: 2011, Volume: 100, Issue: 4, Pages: 1005-1013 |
| ISSN: | 1542-0086 |
| DOI: | 10.1016/j.bpj.2010.12.3697 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.bpj.2010.12.3697 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006349510052136 
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| Author Notes: | Xiaochuan (Edward) Li, Larry S. Tobacman, Ji Young Mun, Roger Craig, Stefan Fischer, and William Lehman |
| Summary: | Electron microscopy and fiber diffraction studies of reconstituted F-actin-tropomyosin filaments reveal the azimuthal position of end-to-end linked tropomyosin molecules on the surface of actin. However, the longitudinal z-position of tropomyosin along F-actin is still uncertain. Without this information, atomic models of F-actin-tropomyosin filaments, free of constraints imposed by troponin or other actin-binding proteins, cannot be formulated, and thus optimal interfacial contacts between actin and tropomyosin remain unknown. Here, a computational search assessing electrostatic interactions for multiple azimuthal locations, z-positions, and pseudo-rotations of tropomyosin on F-actin was performed. The information gleaned was used to localize tropomyosin on F-actin, yielding an atomic model characterized by protein-protein contacts that primarily involve clusters of basic amino acids on actin subdomains 1 and 3 juxtaposed against acidic residues on the successive quasi-repeating units of tropomyosin. A virtually identical model generated by docking F-actin and tropomyosin atomic structures into electron microscopy reconstructions of F-actin-tropomyosin validated the above solution. Here, the z-position of tropomyosin alongside F-actin was defined by matching the seven broad and narrow motifs that typify tropomyosin's twisting superhelical coiled-coil to the wide and tapering tropomyosin densities seen in surface views of F-actin-tropomyosin reconstructions. The functional implications of the F-actin-tropomyosin models determined in this work are discussed. |
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| Item Description: | Gesehen am 25.08.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1542-0086 |
| DOI: | 10.1016/j.bpj.2010.12.3697 |