Structural Insights on the Obscurin-Binding Domains in Titin

Introduction: The giant muscular proteins titin and obscurin bind to each other at the Zdisk during muscle development. This binding event is mediated through two domains from each protein: ZIg9/10 from titin and Ig58/59 from obscurin. This interaction helps stabilize and organize the sarcomere; ablation of this binding leads to muscular dystrophy. Objective: Here we solve the high-resolution solution structure of titin ZIg10 and further delineate which sections of titin bind to obscurin. Materials and Methods: Solution NMR, Circular Dichroism, and SEC-MALS were used to biophysically characterize the titin domains involved in this titin-obscurin interaction. Results and Conclusion: We present the high-resolution solution structure of titin ZIg10. Additionally, we show that titin ZIg9 drives the titin-obscurin interaction, while ZIg10 does not actively participate in the titin-obscurin interaction but instead acts to stabilize ZIg9.