8BNQ

Crystal structure of the FnIII-tandem A84-A86 from the A-band of titin

Summary for 8BNQ

• Entry DOI: 10.2210/pdb8bnq/pdb
• Descriptor: Titin, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: titin, muscle, a-band, structural protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 67210.50

Authors

Zacharchenko, T.,Fleming, J.R.,Mayans, O. (deposition date: 2022-11-14, release date: 2023-04-12, Last modification date: 2024-02-07)

Primary citation

Fleming, J.R.,Muller, I.,Zacharchenko, T.,Diederichs, K.,Mayans, O.
Molecular insights into titin's A-band.
J.Muscle Res.Cell.Motil., 44:255-270, 2023

PubMed Abstract: 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.

PubMed: 37258982
DOI: 10.1007/s10974-023-09649-1

Experimental method

X-RAY DIFFRACTION (2.3 Å)