Molecular insights into titin’s A-band
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The thick filament-associated A-band region of titin is a highly repetitive component of the titin chain with important scaffolding properties that support thick filament assembly. It also has a demonstrated link to human disease. Despite its functional significance, it remains a largely uncharacterized part of the titin protein. Here, we have performed an analysis of sequence and structure conservation of A-band titin, with emphasis on poly-FnIII tandem components. Specifically, we have applied multi-dimensional sequence pairwise similarity analysis to FnIII domains and complemented this with the crystallographic elucidation of the 3D-structure of the FnIII-triplet A84-A86 from the fourth long super-repeat in the C-zone (C4). Structural models serve here as templates to map sequence conservation onto super-repeat C4, which we show is a prototypical representative of titin’s C-zone. This templating identifies positionally conserved residue clusters in C super-repeats with the potential of mediating interactions to thick-filament components. Conservation localizes to two super-repeat positions: Ig domains in position 1 and FnIII domains in position 7. The analysis also allows conclusions to be drawn on the conserved architecture of titin’s A-band, as well as revisiting and expanding the evolutionary model of titin’s A-band.
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FLEMING, Jennifer R., Iljas MÜLLER, Kay DIEDERICHS, Olga MAYANS, Thomas ZACHARCHENKO, 2023. Molecular insights into titin’s A-band. In: Journal of Muscle Research and Cell Motility. Springer. 2023, 44(4), pp. 255-270. ISSN 0142-4319. eISSN 1573-2657. Available under: doi: 10.1007/s10974-023-09649-1BibTex
@article{Fleming2023-05-31Molec-67061, year={2023}, doi={10.1007/s10974-023-09649-1}, title={Molecular insights into titin’s A-band}, number={4}, volume={44}, issn={0142-4319}, journal={Journal of Muscle Research and Cell Motility}, pages={255--270}, author={Fleming, Jennifer R. and Müller, Iljas and Diederichs, Kay and Mayans, Olga and Zacharchenko, Thomas} }
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