α-Actinin/titin interaction: A dynamic and mechanically stable cluster of bonds in the muscle Z-disk

M Grison, U Merkel, J Kostan… - Proceedings of the …, 2017 - National Acad Sciences
M Grison, U Merkel, J Kostan, K Djinović-Carugo, M Rief
Proceedings of the National Academy of Sciences, 2017National Acad Sciences
Stable anchoring of titin within the muscle Z-disk is essential for preserving muscle integrity
during passive stretching. One of the main candidates for anchoring titin in the Z-disk is the
actin cross-linker α-actinin. The calmodulin-like domain of α-actinin binds to the Z-repeats of
titin. However, the mechanical and kinetic properties of this important interaction are still
unknown. Here, we use a dual-beam optical tweezers assay to study the mechanics of this
interaction at the single-molecule level. A single interaction of α-actinin and titin turns out to …
Stable anchoring of titin within the muscle Z-disk is essential for preserving muscle integrity during passive stretching. One of the main candidates for anchoring titin in the Z-disk is the actin cross-linker α-actinin. The calmodulin-like domain of α-actinin binds to the Z-repeats of titin. However, the mechanical and kinetic properties of this important interaction are still unknown. Here, we use a dual-beam optical tweezers assay to study the mechanics of this interaction at the single-molecule level. A single interaction of α-actinin and titin turns out to be surprisingly weak if force is applied. Depending on the direction of force application, the unbinding forces can more than triple. Our results suggest a model where multiple α-actinin/Z-repeat interactions cooperate to ensure long-term stable titin anchoring while allowing the individual components to exchange dynamically.
National Acad Sciences