ArticleNature communications2024
Autoinhibition and activation of myosin VI revealed by its cryo-EM structure.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 12 citations in OpenAlex.
- Tonotopic specialization of MYO7A isoforms in auditory hair cells.Nature communications · 2026Article
- TOM1 family proteins: from cargo sorting to immune dysregulation and cancer.Cell communication and signaling : CCS · 2026Review
- Plasmodium falciparum PfMyoF contains a Rab-like tail domain and associates with perinuclear membrane trafficking proteins.Communications biology · 2026Article
- Coordinated Arp2/3-mediated actin branching and myosin-dependent force generation in membrane-cytoskeleton remodeling.Frontiers in physiology · 2026Review
- Identification of LncRNA Mhrt as a potential biomarker for preventing the progression of Myocardial Ischemia-Reperfusion Injury through bioinformatics and experimental validation.BMC cardiovascular disorders · 2025Article
- Structure-Guided Stapling of Dimeric Conformations and Linker Engineering Enhance Thermostability and Fine-Tune Activity of Bispecific VHH Cytokine Agonists.Antibodies (Basel, Switzerland) · 2025Article
- Cardiolipin membranes drive Myosin VI activation, oligomerization, and processive cargo transport.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Select autosomal dominant DFNA11 deafness variants activate Myo7A targeting in epithelial cells.Journal of cell science · 2025Article
- Proteomic profiling of the serological response to a chemically-inactivated nodavirus vaccine in European sea bass Dicentrarchus labrax.Veterinary research communications · 2025Article
- Actin from within - how nuclear myosins and actin regulate nuclear architecture and mechanics.Journal of cell science · 2025Review
- Expression, Purification, and In Vitro Analysis of Myosin.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Pathophysiology of human hearing loss associated with variants in myosins.Frontiers in physiology · 2024Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Myosin VI is the only molecular motor that moves towards the minus end along actin filaments. Numerous cellular processes require myosin VI and tight regulations of the motor's activity. Defects in myosin VI activity are known to cause genetic diseases such as deafness and cardiomyopathy. However, the molecular mechanisms underlying the activity regulation of myosin VI remain elusive. Here, we determined the high-resolution cryo-electron microscopic structure of myosin VI in its autoinhibited state. Our structure reveals that autoinhibited myosin VI adopts a compact, monomeric conformation via extensive interactions between the head and tail domains, orchestrated by an elongated single-α-helix region resembling a "spine". This autoinhibited structure effectively blocks cargo binding sites and represses the motor's ATPase activity. Certain cargo adaptors such as GIPC can release multiple inhibitory interactions and promote motor activity, pointing to a cargo-mediated activation of the processive motor. Moreover, our structural findings allow rationalization of disease-associated mutations in myosin VI. Beyond the activity regulation mechanisms of myosin VI, our study also sheds lights on how activities of other myosin motors such as myosin VII and X might be regulated.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.