GO:0017022 myosin binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0017022 myosin binding is a molecular function defined as binding to a myosin, a superfamily of ATP-dependent motor proteins that move along actin filaments.
• Myosin binding underlies fundamental processes including muscle contraction, cytokinesis, and intracellular transport, as reviewed in the actomyosin complex.
• Key myosin-binding proteins include calponin, caldesmon, myosin binding protein-C, and von Willebrand factor, each regulating distinct aspects of myosin activity [5,7,8,1].
• Dysregulation of myosin binding is linked to cardiovascular diseases such as hypertrophic cardiomyopathy and coagulation disorders [8,1].
• Advanced methods such as cryo-electron tomography, super-resolution microscopy, and molecular dynamics simulations are used to study myosin binding [8,2,6].
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) enable functional dissection of myosin-binding proteins in health and disease.
Description
Myosin binding (GO:0017022) is a molecular function that encompasses the binding to myosin, a superfamily of molecular motor proteins that convert chemical energy from ATP hydrolysis into mechanical force along actin filaments. This function is central to numerous cellular processes, including muscle contraction, cell division, and vesicle transport, where myosin interacts with a diverse array of binding partners to execute its roles. Understanding myosin binding is therefore critical for deciphering the molecular mechanisms of motility and force generation in cells. The actomyosin complex, formed by myosin binding to actin and regulatory proteins, serves as a paradigm for studying mechanochemical coupling. Moreover, myosin-binding proteins such as calponin and caldesmon modulate the ATPase cycle of myosin, influencing contractility in smooth muscle and non-muscle cells [5,7]. In striated muscle, myosin binding protein-C links myosin and actin filaments, contributing to sarcomere stability and function. These interactions are not only fundamental to physiology but also implicated in a range of diseases, from cardiomyopathies to bleeding disorders [8,1]. Consequently, researchers across disciplines investigate myosin binding to uncover therapeutic targets and to understand how mutations in myosin-binding proteins lead to pathology. This article provides a comprehensive overview of the definition, mechanisms, key genes, and research methodologies associated with GO:0017022, based on authoritative QuickGO data and verified PubMed literature.
myosin binding At A Glance
| GO ID | GO:0017022 |
|---|---|
| GO term | myosin binding |
| Ontology | molecular_function |
| Synonym | myosin phosphatase myosin binding |
| Major function | Binding to myosin motor proteins, regulating their activity and interactions with actin. |
| Related processes | Muscle contraction, cytokinesis, intracellular transport. |
| Key examples | Calponin, caldesmon, myosin binding protein-C, von Willebrand factor [5,7,8,1]. |
| Disease relevance | Hypertrophic cardiomyopathy, coagulation disorders [8,1]. |
| Research methods | Cryo-electron tomography, super-resolution microscopy, molecular dynamics [8,2,6]. |
What Is GO:0017022?
According to the Gene Ontology, myosin binding (GO:0017022) is defined as the binding to a myosin; myosins are any of a superfamily of molecular motor proteins that bind to actin and use the energy of ATP hydrolysis to generate force and movement along actin filaments. In essence, it describes the molecular interaction between a protein or other molecule and a myosin motor, which is essential for various cellular functions ranging from muscle contraction to intracellular transport.
Why Is myosin binding Important in Cell Biology?
Myosin binding is fundamentally important because it governs the activity and regulation of myosin motors, which are indispensable for force generation and movement in all eukaryotic cells. Proper myosin binding ensures accurate muscle contraction, cell division, and cargo transport, while its dysregulation contributes to severe human diseases, including cardiovascular disorders and bleeding abnormalities [8,1]. Thus, studying myosin binding provides insights into basic cell biology and offers potential targets for therapeutic intervention.
• Essential for muscle contraction: myosin binding to actin and regulatory proteins drives sarcomere shortening.
• Regulates smooth muscle contractility via calponin and caldesmon, which modulate myosin ATPase activity [5,7].
• Critical for cardiac function: myosin binding protein-C mutations cause hypertrophic cardiomyopathy.
• Involved in hemostasis: von Willebrand factor binding to myosin assists in coagulation.
• Plays a role in cell division: myosin binding proteins are required for cytokinesis.
• Implicated in cancer: altered myosin binding can affect cell migration and invasion.
• Target for drug discovery: small molecules modulating myosin binding are explored for heart failure.
• Reveals molecular mechanisms of motor proteins through advanced imaging and simulation [2,6].
• Provides insights into genetic diseases: mutations in myosin-binding proteins lead to pathologies.
• Enables synthetic biology: engineered myosin-binding domains can control cellular processes.
Molecular Mechanism of myosin binding
Binding to myosin motor domain
In simple terms: Proteins bind directly to the part of myosin that moves along actin.
Myosin-binding proteins typically interact with the motor domain or tail region of myosin, influencing its ATPase cycle and motility. For example, caldesmon binds to both actin and myosin, affecting elementary steps in the ATPase cycle. Similarly, calponin binds to myosin and inhibits its ATPase activity in smooth muscle. These interactions are critical for regulating contractility.
Regulation of ATPase cycle
In simple terms: Binding partners can speed up or slow down the myosin motor's energy use.
Myosin binding proteins modulate the rate of ATP hydrolysis and product release. Caldesmon, for instance, inhibits the ATPase cycle by interfering with phosphate release. In cardiac muscle, myosin binding protein-C (MyBP-C) modulates cross-bridge cycling kinetics, as revealed by cryo-electron tomography. These regulatory effects fine-tune muscle contraction and relaxation.
Structural basis of interaction
In simple terms: The shape of myosin and its partners determines how they fit together.
High-resolution structures and simulations have elucidated the binding interfaces. Molecular dynamics simulations of human β-cardiac myosin revealed binding pocket dynamics along the recovery stroke, which are essential for nucleotide binding and force generation. Super-resolution microscopy has visualized cooperative and competitive binding of anti-myosin tail antibodies, providing insights into myosin filament assembly.
Cofactors and post-translational modifications
In simple terms: Other molecules and chemical tags can affect how myosin binds to its partners.
Phosphorylation of myosin regulatory light chain enhances its interaction with binding proteins, although specific references are not provided here. Additionally, ankyrin repeat proteins inhibit membrane binding of endocytic myosin-1s, demonstrating that accessory factors can regulate myosin binding. These modifications add layers of control to myosin function.
Role in actomyosin complex assembly
In simple terms: Myosin binding helps assemble the machinery that contracts muscles and moves cells.
The actomyosin complex is a dynamic assembly of myosin, actin, and associated proteins. Myosin binding protein-C links myosin and actin filaments in cardiac muscle, contributing to sarcomere integrity. Von Willebrand factor binding to myosin assists in coagulation, highlighting the diverse roles of myosin binding outside muscle. These interactions are vital for both structural stability and functional output.
Key Genes Involved in GO:0017022 myosin binding
The following genes encode proteins that bind to myosin and are central to the function of GO:0017022, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| MYH7 | Encodes β-cardiac myosin heavy chain; binding pocket dynamics affect motor function | Mutations cause hypertrophic cardiomyopathy; target for drug development |
| MYBPC3 | Encodes myosin binding protein-C; links myosin and actin in sarcomeres | Mutations lead to hypertrophic cardiomyopathy; studied via cryo-ET |
| CNN1 | Encodes calponin; binds myosin and inhibits ATPase in smooth muscle | Regulates smooth muscle contractility; potential target in vascular diseases |
| CALD1 | Encodes caldesmon; binds actin and myosin, modulates ATPase cycle | Involved in smooth muscle regulation; studied for contractile dysfunction |
| VWF | Encodes von Willebrand factor; binds myosin to assist coagulation | Defects cause von Willebrand disease; role in hemostasis |
| MYO1 | Encodes myosin-1; membrane binding regulated by ankyrin repeat proteins | Endocytic myosin-1s are studied for membrane trafficking |
| MYH9 | Encodes non-muscle myosin heavy chain IIA; binds various partners | Mutations cause MYH9-related disorders; model for platelet function |
| ACTN1 | Encodes alpha-actinin; binds myosin and actin, crosslinks filaments | Studied in cytoskeletal organization and cell adhesion |
| TPM1 | Encodes tropomyosin; binds actin and modulates myosin binding | Mutations linked to cardiomyopathy; affects actomyosin regulation |
| TNNT2 | Encodes cardiac troponin T; regulates myosin binding to actin | Mutations cause hypertrophic cardiomyopathy; target for functional studies |
| MYL2 | Encodes regulatory light chain of myosin; modulates myosin binding | Phosphorylation affects contractility; studied in heart failure |
| MYL3 | Encodes essential light chain of myosin; stabilizes myosin structure | Mutations associated with cardiomyopathy; affects motor function |
| MYO5B | Encodes myosin Vb; binds Rab proteins and cargo | Defects cause microvillus inclusion disease; studied in transport |
| MYO7A | Encodes myosin VIIA; binds harmonin and cadherins | Mutations cause Usher syndrome; studied in hearing and vision |
| MYO6 | Encodes myosin VI; binds adaptor proteins for endocytosis | Involved in deafness and cancer; studied for cargo binding |
| MYO10 | Encodes myosin X; binds integrins and actin | Roles in cell migration and filopodia; cancer research |
| MYO18A | Encodes myosin XVIIIA; binds Golgi membranes | Studied in Golgi organization and secretion |
| MYO19 | Encodes myosin XIX; binds mitochondria | Involved in mitochondrial dynamics; emerging research area |
How Is myosin binding Regulated?
Myosin binding is regulated at multiple levels, including post-translational modifications of myosin and its binding partners, such as phosphorylation of the regulatory light chain, which can enhance or inhibit interactions. Additionally, accessory proteins like ankyrin repeat proteins can inhibit membrane binding of endocytic myosin-1s. Calcium signaling via calmodulin also modulates myosin binding in smooth muscle through caldesmon and calponin [5,7]. These regulatory mechanisms ensure precise control of myosin activity in response to cellular signals.
myosin binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| MYBPC3 | Hypertrophic cardiomyopathy | Knock-in mouse model with patient mutation; iPSC-derived cardiomyocytes |
| MYH7 | Hypertrophic cardiomyopathy, dilated cardiomyopathy | Point mutation knock-in in hiPSCs; CRISPR-edited cardiac organoids |
| VWF | Von Willebrand disease, bleeding | Knockout zebrafish; overexpression in endothelial cells |
| CNN1 | Smooth muscle dysfunction, hypertension | Knockout mouse; siRNA in vascular smooth muscle cells |
| CALD1 | Smooth muscle dysfunction, asthma | Conditional knockout mouse; CRISPR knockout in airway smooth muscle |
Hypertrophic cardiomyopathy
Mutations in MYBPC3, which encodes myosin binding protein-C, are a leading cause of hypertrophic cardiomyopathy. Cryo-electron tomography has revealed that MyBP-C links myosin and actin filaments, and its dysfunction disrupts sarcomere organization, leading to cardiac hypertrophy. Similarly, mutations in MYH7, the β-cardiac myosin heavy chain, alter binding pocket dynamics and motor function, contributing to disease.
Coagulation disorders
Von Willebrand factor (VWF) binding to myosin assists in coagulation, and defects in this interaction can lead to bleeding disorders such as von Willebrand disease. Studies have shown that VWF binds to myosin exposed at sites of vascular injury, facilitating platelet adhesion and clot formation.
Smooth muscle dysfunction
Calponin and caldesmon regulate smooth muscle contraction by binding to myosin and modulating its ATPase activity. Alterations in their expression or function are implicated in conditions such as hypertension and asthma, where smooth muscle contractility is dysregulated [5,7].
Endocytic trafficking defects
Myosin-1 motors are involved in endocytosis, and their membrane binding is inhibited by ankyrin repeat proteins. Disruption of this regulation can impair vesicle trafficking, contributing to diseases such as microvillus inclusion disease and certain neuropathies.
From myosin binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of MYBPC3 affect sarcomere structure? | MYBPC3 knockout hiPSCs differentiated to cardiomyocytes |
| How does a specific MYH7 mutation alter myosin binding? | Point mutation knock-in in HEK293 or hiPSCs |
| Can overexpression of CNN1 rescue smooth muscle defects? | Overexpression of CNN1 in primary smooth muscle cells |
| Where does VWF bind myosin in vivo? | Tagged knock-in of VWF in zebrafish or mouse |
| What is the interactome of myosin-binding proteins? | Knock-in of APEX2 tag into MYBPC3 locus for proximity labeling |
| Does ankyrin repeat protein regulate myosin-1 membrane binding? | Knockout of ankyrin repeat gene in epithelial cells |
How to Study the myosin binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Cryo-electron tomography | 3D structure of actomyosin complex in situ | Visualizing MyBP-C links in cardiac muscle |
| Molecular dynamics simulation | Binding pocket dynamics and conformational changes | Studying recovery stroke of β-cardiac myosin |
| Super-resolution microscopy | Spatial distribution and binding cooperativity | Analyzing anti-myosin antibody binding |
| Co-sedimentation assay | Direct binding affinity between myosin and partners | Quantifying caldesmon-myosin interaction |
| ATPase activity assay | Enzymatic activity of myosin | Assessing calponin inhibition |
| CRISPR knockout | Loss-of-function phenotypes | Studying MYBPC3 in cardiomyocytes |
| Proximity labeling (APEX2) | Interactome of myosin-binding proteins | Identifying novel binding partners in vivo |
| Live-cell imaging | Dynamic localization of myosin and partners | Tracking endocytic myosin-1 |
Structural biology approaches
Cryo-electron tomography has been used to visualize myosin binding protein-C linking myosin and actin filaments in intact cardiac muscle, providing near-atomic resolution of the actomyosin complex. Molecular dynamics simulations complement these studies by revealing binding pocket dynamics along the recovery stroke of human β-cardiac myosin.
Super-resolution microscopy
Super-resolution microscopy techniques such as STORM have been employed to study cooperative and competitive binding of anti-myosin tail antibodies, offering insights into myosin filament assembly and the spatial organization of myosin-binding proteins.
Biochemical assays
In vitro binding assays, including co-sedimentation and surface plasmon resonance, are used to quantify interactions between myosin and its binding partners. For example, caldesmon binding to actin and myosin and its effects on ATPase cycle steps have been characterized using such methods.
Functional studies in cells
Live-cell imaging and genetic manipulation (e.g., siRNA, CRISPR knockout) allow researchers to assess the functional consequences of disrupting myosin binding. Studies on endocytic myosin-1s and ankyrin repeat proteins have used these approaches to demonstrate regulation of membrane binding.
How CRISPR Can Be Used to Study GO:0017022 myosin binding
Knockout
CRISPR knockout of genes encoding myosin-binding proteins, such as MYBPC3 or CNN1, allows researchers to assess loss-of-function phenotypes. For example, MYBPC3 knockout hiPSCs differentiated into cardiomyocytes model hypertrophic cardiomyopathy and reveal sarcomere disorganization. Knockout of endocytic myosin-1 in epithelial cells can elucidate its role in membrane trafficking.
Point Mutation
Introducing disease-associated point mutations (e.g., in MYH7 or MYBPC3) via CRISPR base editing or HDR enables precise modeling of altered myosin binding. Such models help determine how specific mutations affect motor function and contribute to cardiomyopathy [6,8].
Knock-in
Knock-in of tags (e.g., GFP, APEX2) into endogenous myosin-binding protein loci allows visualization and interactome analysis. Tagged MyBP-C knock-in in cardiomyocytes can reveal its dynamic localization and binding partners in live cells.
Overexpression
Overexpression of myosin-binding proteins, such as calponin or caldesmon, in cell lines or primary cells can test gain-of-function effects on contractility and myosin ATPase activity. This approach is useful for rescue experiments and for studying regulatory mechanisms [5,7].
How EDITGENE Supports myosin binding Research
Researchers studying myosin binding-related genes often need to determine whether a candidate gene is causally involved in a specific cellular process or disease. EDITGENE provides comprehensive CRISPR-based services to generate precisely engineered cell models, enabling functional validation of myosin-binding proteins and their roles in health and disease.
Contact EDITGENE today to design your custom CRISPR model for myosin binding research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RALA Knockout HEK293 Cell Line | EDJ-KQ1248 | Human | 5898 | Details Get a Quote |
| CNGA3 Knockout HEK293 Cell Line | EDJ-KQ1802 | Human | 1261 | Details Get a Quote |
| CALD1 Knockout HEK293 Cell Line | EDJ-KQ1980 | Human | 800 | Details Get a Quote |
| USH2A Knockout HEK293 Cell Line | EDJ-KQ2141 | Human | 7399 | Details Get a Quote |
| GIPC1 Knockout HEK293 Cell Line | EDJ-KQ2197 | Human | 10755 | Details Get a Quote |
| TRPM7 Knockout HEK293 Cell Line | EDJ-KQ2654 | Human | 54822 | Details Get a Quote |
| DMD Knockout HEK293 Cell Line | EDJ-KQ3154 | Human | 1756 | Details Get a Quote |
| ACTA1 Knockout HEK293 Cell Line | EDJ-KQ3339 | Human | 58 | Details Get a Quote |
| ACTC1 Knockout HEK293 Cell Line | EDJ-KQ3854 | Human | 70 | Details Get a Quote |
| NPHS1 Knockout HEK293 Cell Line | EDJ-KQ3876 | Human | 4868 | Details Get a Quote |
| MYBPC3 Knockout HEK293 Cell Line | EDJ-KQ5279 | Human | 4607 | Details Get a Quote |
| MYBPC1 Knockout HEK293 Cell Line | EDJ-KQ5281 | Human | 4604 | Details Get a Quote |
| STX1A Knockout HEK293 Cell Line | EDJ-KQ5860 | Human | 6804 | Details Get a Quote |
| HAP1 Knockout HEK293 Cell Line | EDJ-KQ6426 | Human | 9001 | Details Get a Quote |
| ARFGEF1 Knockout HEK293 Cell Line | EDC07529 | Human | 10565 | Details Get a Quote |
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Frequently Asked Questions About myosin binding
What is GO:0017022 myosin binding?
GO:0017022 is a Gene Ontology molecular function term defined as binding to a myosin, a superfamily of ATP-dependent motor proteins that move along actin filaments.
What genes are involved in myosin binding?
Key genes include MYH7, MYBPC3, CNN1, CALD1, VWF, and various MYO genes encoding myosin motors and their binding partners [6,8,5,7,1,3].
How is myosin binding studied?
Common methods include cryo-electron tomography, super-resolution microscopy, molecular dynamics simulations, and biochemical binding assays [8,2,6,7].
Why is myosin binding important for muscle contraction?
Myosin binding proteins such as MyBP-C and caldesmon regulate the interaction between myosin and actin, which is essential for force generation during muscle contraction [8,7].
What diseases are associated with defects in myosin binding?
Mutations in MYBPC3 and MYH7 cause hypertrophic cardiomyopathy, while VWF defects lead to bleeding disorders; calponin and caldesmon dysregulation is linked to smooth muscle diseases [8,6,1,5,7].
Can CRISPR be used to study myosin binding?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models allow functional dissection of myosin-binding proteins in various cell types [8,3].
What is the role of myosin binding protein-C?
Myosin binding protein-C (encoded by MYBPC3) links myosin and actin filaments in cardiac sarcomeres and regulates cross-bridge cycling; its mutations cause hypertrophic cardiomyopathy.
How does caldesmon regulate myosin binding?
Caldesmon binds to both actin and myosin and inhibits the ATPase cycle, thereby modulating smooth muscle contractility.
What is the synonym for GO:0017022?
The synonym is myosin phosphatase myosin binding.
Which model systems are used to study myosin binding?
Model systems include hiPSC-derived cardiomyocytes, knockout mice, zebrafish, and various cell lines engineered with CRISPR [8,1,3].
Conclusion
Myosin binding (GO:0017022) is a fundamental molecular function that governs the activity of myosin motors in diverse cellular processes, from muscle contraction to intracellular transport. Dysregulation of myosin-binding proteins is implicated in severe diseases, including cardiomyopathies and bleeding disorders. Advanced structural and functional techniques, combined with CRISPR-based models, continue to unravel the mechanistic details of these interactions. EDITGENE provides comprehensive services to support research on myosin binding, from gene knockout to library screening, empowering discoveries that may lead to novel therapeutics.
References
- 1. Flood VH et al.. 2020. von Willebrand factor binding to myosin assists in coagulation.. Blood Adv 4(1):174-180 PMID: 31935285
- 2. Quedan D et al.. 2023. Cooperative & competitive binding of anti-myosin tail antibodies revealed by super-resolution microscopy.. Arch Biochem Biophys 747:109753 PMID: 37714251
- 3. Willet AH et al.. 2023. Membrane binding of endocytic myosin-1s is inhibited by a class of ankyrin repeat proteins.. Mol Biol Cell 34(11):br17 PMID: 37531259
- 4. Pepper I et al.. 2022. Actomyosin Complex.. Subcell Biochem 99:421-470 PMID: 36151385
- 5. el-Mezgueldi M. 1996. Calponin.. Int J Biochem Cell Biol 28(11):1185-9 PMID: 9022277
- 6. Akter F et al.. 2023. Binding pocket dynamics along the recovery stroke of human β-cardiac myosin.. PLoS Comput Biol 19(5):e1011099 PMID: 37200380
- 7. Chalovich JM et al.. 1998. Caldesmon: binding to actin and myosin and effects on elementary steps in the ATPase cycle.. Acta Physiol Scand 164(4):427-35 PMID: 9887966
- 8. Huang X et al.. 2023. Cryo-electron tomography of intact cardiac muscle reveals myosin binding protein-C linking myosin and actin filaments.. J Muscle Res Cell Motil 44(3):165-178 PMID: 37115473
