Disulfide isomerization reactions in titin immunoglobulin domains enable a mode of protein elasticity
The authors describe a new mode of protein elasticity based on force-triggered disulfide isomerization reactions. This mechanism is hypothesized to set the mechanical properties of titin, a giant muscle protein key to the mechanical output of striated muscle. Image licensed under CC BY NC ND 2018.
Giganti D, Yan K, Badilla CL, Fernandez JM, Alegre-Cebollada J.
Nat Commun 2018 Jan; 9: 185.
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.
PubMed: 29330363. Doi: 10.1038/s41467-017-02528-7. free PMC article
