Evidence for the oligomeric state of 'elastic' titin in muscle sarcomeres |
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Authors: | Houmeida Ahmed Baron Andy Keen Jeff Khan G Nasir Knight Peter J Stafford Walter F Thirumurugan Kavitha Thompson Beatrix Tskhovrebova Larissa Trinick John |
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Institution: | 1 Institute for Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK 2 Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK 3 Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA |
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Abstract: | The giant protein titin has important roles in muscle sarcomere integrity, elasticity and contractile activity. The key role in elasticity was highlighted in recent years by single-molecule mechanical studies, which showed a direct relationship between the non-uniform structure of titin and the hierarchical mechanism of its force-extension behavior. Further advances in understanding mechanisms controlling sarcomere structure and elasticity require detailed knowledge of titin arrangement and interactions in situ. Here we present data on the structure and self-interactive properties of an ∼ 290 kDa (∼ 100 nm long) tryptic fragment from the I-band part of titin that is extensible in situ. The fragment includes the conserved ‘distal’ tandem Ig segment of the molecule and forms side-by-side oligomers with distinctive 4 nm cross-striations. Comparisons between these oligomers and the end filaments seen at the tips of native thick filaments indicate identical structure. This shows that end-filaments are formed by the elastic parts of six titin molecules connecting each end of the thick filament to the Z-line. Self-association of elastic titin into stiff end-filaments adds a further hierarchical level in the mechanism of titin extensibility in muscle cells. Self-association of this part of titin may be required to prevent interference of the individual flexible molecules with myosin cross-bridges interacting with actin. |
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Keywords: | Fn fibronectin AFM atomic force spectroscopy EDTA ethylenediaminetetraacetic acid |
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