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  The shape and flexibility of tropomyosin coiled coils: implications for actin filament assembly and regulation

Li, X. E., Holmes, K. C., Lehman, W., Jung, H. S., & Fischer, S. (2010). The shape and flexibility of tropomyosin coiled coils: implications for actin filament assembly and regulation. Journal of Molecular Biology (London), 395(2), 327-339. doi:10.1016/j.jmb.2009.10.060.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-8104-C Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-8105-A
Genre: Journal Article
Alternative Title : The shape and flexibility of tropomyosin coiled coils: implications for actin filament assembly and regulation

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 Creators:
Li, Xiaochuan Edward, Author
Holmes, Kenneth C.1, Author              
Lehman, William, Author
Jung, Hyun Suk, Author
Fischer, Stefan, Author
Affiliations:
1Emeritus Group Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_1497712              

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Free keywords: actin; tropomyosin; coiled coils; electron microscopy; molecular dynamics
 Abstract: Wrapped superhelically around actin filaments, the coiled-coil alpha-helices of tropomyosin regulate muscle contraction by cooperatively blocking or exposing myosin-binding sites on actin. In non-muscle cells, tropomyosin additionally controls access of actin-binding proteins involved in cytoskeletal actin filament maintenance and remodeling. Tropomyosin's global shape and flexibility play a key role in the assembly, maintenance, and regulatory switching of thin filaments yet remain insufficiently characterized. Here, electron microscopy and molecular dynamics simulations yielded conformations of tropomyosin closely resembling each other. The electron microscopy and simulations show that isolated tropomyosin has an average curved conformation with a design well matched to its superhelical shape on F-actin. In addition, they show that tropomyosin bends smoothly yet anisotropically about its distinctive helically curved conformation, without any signs of unfolding, chain separation, localized kinks, or joints. Previous measurements, assuming tropomyosin to be straight on average, mistakenly suggested considerable flexibility (with persistence lengths only approximately 3 times the protein's length). However, taking the curved average structure determined here as reference for the flexibility measurements yields a persistence length of approximately 12 lengths, revealing that tropomyosin actually is semirigid. Corresponding simulation of a triple mutant (A74L-A78V-A81L) with weak actin affinity shows that it lacks shape complementarity to F-actin. Thus, tropomyosin's pre-shaped semirigid architecture is essential for the assembly of actin filaments. Further, we propose that once bound to thin filaments, tropomyosin will be stiff enough to act as a cooperative unit and move on actin in a concerted way between known regulatory states.

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Language(s): eng - English
 Dates: 2009-08-132009-10-272009-10-312010-01-15
 Publication Status: Published in print
 Pages: 13
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 Table of Contents: -
 Rev. Method: Peer
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Title: Journal of Molecular Biology (London)
  Other : J Mol Biol
Source Genre: Journal
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Publ. Info: London : Academic Press
Pages: - Volume / Issue: 395 (2) Sequence Number: - Start / End Page: 327 - 339 Identifier: ISSN: 0022-2836
CoNE: /journals/resource/954922646042