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

Marco Grison; Ulrich Merkel; Julius Kostan; Kristina Djinović-Carugo; Matthias Rief

doi:10.1073/pnas.1612681114

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

Marco Grison, Ulrich Merkel, Julius Kostan, Kristina Djinović-Carugo, Matthias Rief

Chair of Biophysics

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

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 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.

Original language	English
Pages (from-to)	1015-1020
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	114
Issue number	5
DOIs	https://doi.org/10.1073/pnas.1612681114
State	Published - 31 Jan 2017

Keywords

Optical tweezers
Titin Z-repeats
Z-disk mechanics
α-actinin

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

abstract = "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 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.",

keywords = "Optical tweezers, Titin Z-repeats, Z-disk mechanics, α-actinin",

author = "Marco Grison and Ulrich Merkel and Julius Kostan and Kristina Djinovi{\'c}-Carugo and Matthias Rief",

note = "Funding Information: This work was supported by Marie Curie Initial Training Network MUZIC Grant 238423; Austrian Science Fund Projects I525, I1593, P22276, and P19060; Federal Ministry of Economy, Family and Youth through the initiative, {"}Laura Bassi Centres of Expertise{"} (K.D.C.); Center of Optimized Structural Studies Grant 253275 (to J.K.); the University of Vienna; and Deutsche Forschungsgemeinschaft Grant FOR 1352 P8 (to M.R.).",

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AU - Grison, Marco

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AU - Kostan, Julius

AU - Djinović-Carugo, Kristina

AU - Rief, Matthias

N1 - Funding Information: This work was supported by Marie Curie Initial Training Network MUZIC Grant 238423; Austrian Science Fund Projects I525, I1593, P22276, and P19060; Federal Ministry of Economy, Family and Youth through the initiative, "Laura Bassi Centres of Expertise" (K.D.C.); Center of Optimized Structural Studies Grant 253275 (to J.K.); the University of Vienna; and Deutsche Forschungsgemeinschaft Grant FOR 1352 P8 (to M.R.).

PY - 2017/1/31

Y1 - 2017/1/31

N2 - 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 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.

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

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