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Updated: Jul 12, 2025
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Dissecting Mechanoenzymatic Properties of Processive Myosins with Ultrafast Force-Clamp Spectroscopy
Published on: July 1, 2021
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How myosin VI traps its off-state, is activated and dimerizes
Louise Canon1, Carlos Kikuti1, Vicente J Planelles-Herrero1
1Structural Motility, UMR 144 CNRS/Curie Institute, PSL Research University, 26 rue d'Ulm, 75258, Paris cedex 05, France.
Nature Communications
|October 23, 2023
Summary
Myosin VI (Myo6) partners differentially control its activity and localization. This regulation is crucial for cellular functions, with specific mutations impacting Myo6 auto-inhibition and dimerization.
Area of Science:
- Cell Biology
- Molecular Motors
- Protein Structure and Function
Background:
- Myosin VI (Myo6) is a unique minus-end directed actin nanomotor essential for various cellular processes.
- Myo6 function depends on precise regulation of its motor activity, including an auto-inhibited off-state and interactions with binding partners.
Purpose of the Study:
- To elucidate the regulatory mechanisms of Myosin VI (Myo6) activity and localization.
- To investigate how different Myo6 partners influence its auto-inhibition, activation, and dimerization.
- To understand the structural basis of Myo6 regulation and the impact of a deafness mutation.
Main Methods:
- Structural biology (crystal structure of the proximal dimerization domain)
- Functional assays to assess Myo6 partner interactions and activation
- Cellular studies in HeLa cells to evaluate endocytosis and dimerization
- Analysis of the L926Q deafness mutation's effect on Myo6 regulation
Main Results:
- Myo6 partners exhibit differential binding and regulatory effects; TOM1 and Dab2 do not bind the off-state, while GIPC1 binding releases auto-inhibition and promotes dimerization.
- The proximal dimerization domain is critical for Myo6 function, as its disruption impairs endocytosis.
- The L926Q deafness mutation disrupts Myo6 auto-inhibition and indirectly affects proximal dimerization.
Conclusions:
- Myosin VI (Myo6) regulation is significantly controlled by its interaction partners, influencing auto-inhibition, localization, and activation.
- Myo6 dimerization is essential for its cellular functions, particularly endocytosis.
- Understanding Myo6 regulation provides insights into the molecular basis of deafness mutations.
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