Figure 1.
![Schematic representation of MARP1 locking titin–N2A to the thin filament. In the “free state” the N2A-segment (region spanning Ig-like [I; red domains] domains 80–83) is unbound to the actin-based thin filament. Under stress conditions, muscles up-regulate MARP1 (black, coiled-coil domain; orange, ankyrin repeats), which binds to the N2A unique sequence (Us; blue) and I81. The N2A–MARP1 complex forms a molecular “glue” that binds to the actin-based thin filament (magenta), locking part of titin‘s I-band spring. This “locked state” increases the extension of titin’s PEVK domain (in yellow, flanked by I83 and I84) during sarcomere stretch, thereby increasing the passive force generated by titin.](https://cdn.rupress.org/rup/content_public/journal/jgp/153/7/10.1085_jgp.202112904/3/jgp_202112904_fig1.png?Expires=1773602310&Signature=Y4kgJAk77KfejuFYSG1CRK3RsVzm1Y~AVGMooTfVGCIftnq0~-0XZgLlbDGln1bSOQrV2cldVvkwBYuG-Xd7q5apeLZRYtvSELm8DaP9-nAHabp70LeHbyD3Ct8GYPHCySSIz9ae~1mQU9SQJxrQFmiMRnxT5nAnOCXSDTOCAWaOstmZ49YlQGfOl37VIpufafgon0exBKD0Da1m1gTt5gjcU0MSENrW4hQOxOjBpbZmtxCq2MW0sUvklch1S76O5to7Yn2QOVykgT9aBY~IRrdYDdjsZwJYXaG6xhJplvob0bxnYucZmsQS3~dR519gy6mrJbZ~9gwFz6NnoRcfNg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Schematic representation of MARP1 locking titin–N2A to the thin filament. In the “free state” the N2A-segment (region spanning Ig-like [I; red domains] domains 80–83) is unbound to the actin-based thin filament. Under stress conditions, muscles up-regulate MARP1 (black, coiled-coil domain; orange, ankyrin repeats), which binds to the N2A unique sequence (Us; blue) and I81. The N2A–MARP1 complex forms a molecular “glue” that binds to the actin-based thin filament (magenta), locking part of titin‘s I-band spring. This “locked state” increases the extension of titin’s PEVK domain (in yellow, flanked by I83 and I84) during sarcomere stretch, thereby increasing the passive force generated by titin.