Molecular insights into titin’s A-band

Olga Mayans (Corresponding), Jennifer Fleming (Lead), Thomas Zacharchenko, Kay Diederichs, Iljas Muller

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)255-270
Number of pages16
JournalJournal of Muscle Research and Cell Motility
Issue number4
Early online date31 May 2023
Publication statusPublished - Dec 2023


  • Pairwise sequence similarity
  • Sequence conservation 3D-mapping
  • Titin evolution
  • X-ray crystallography
  • poly-FnIII tandem


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