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

作者：Grison Marco; Merkel Ulrich; Kostan Julius; Djinovic Carugo Kristina; Rief Matthias^*

来源：Proceedings of the National Academy of Sciences, 2017, 114(5): 1015-1020.

DOI：10.1073/pnas.1612681114

• alpha-actinin
• titin Z-repeats
• Z-disk mechanics
• optical tweezers

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 crosslinker a-actinin. The calmodulin-like domain of alpha-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 alpha-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 alpha-actinin/Z-repeat interactions cooperate to ensure long-term stable titin anchoring while allowing the individual components to exchange dynamically.

• 出版日期2017-1-31