2026-06-14T00:31:59Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/66952024-09-27T09:33:47Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Giganti, David
author
Yan, Kevin
author
Badilla, Carmen L.
author
Fernandez, Julio M.
author
Alegre-Cebollada, Jorge
funder
National Science Foundation (Estados Unidos)
funder
National Institutes of Health (Estados Unidos)
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Fundación ProCNIC
funder
Unión Europea. Comisión Europea
2018-11-22T08:10:54Z
2018-11-22T08:10:54Z
2018
Nat Commun. 2018; 9(1):185
10.1038/s41467-017-02528-7
2041-1723
Nature Communications
29330363
http://hdl.handle.net/20.500.12105/6695
The response of titin to mechanical forces is a major determinant of the function of the heart. When placed under a pulling force, the unstructured regions of titin uncoil while its immunoglobulin (Ig) domains unfold and extend. Using single-molecule atomic force microscopy, we show that disulfide isomerization reactions within Ig domains enable a third mechanism of titin elasticity. Oxidation of Ig domains leads to non-canonical disulfide bonds that stiffen titin while enabling force-triggered isomerization reactions to more extended states of the domains. Using sequence and structural analyses, we show that 21\% of titin's I-band Ig domains contain a conserved cysteine triad that can engage in disulfide isomerization reactions. We propose that imbalance of the redox status of myocytes can have immediate consequences for the mechanical properties of the sarcomere via alterations of the oxidation state of titin domains.
eng
Disulfide isomerization reactions in titin immunoglobulin domains enable a mode of protein elasticity
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DisulfideIsomerizationReactionsTitin_2018.pdf
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DisulfideIsomerizationReactionsTitin_2018_MOESM1_ESM.pdf
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DisulfideIsomerizationReactionsTitin_2018.pdf.txt
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https://repisalud.isciii.es/bitstreams/f0efbe56-a7ca-4576-9021-3c805e14320c/download
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DisulfideIsomerizationReactionsTitin_2018_MOESM1_ESM.pdf.txt