Mechanochemical Function of Myosin II: Investigation into the Recovery Stroke and ATP Hydrolysis

Myosins are one of the largest protein superfamilies with 24 classes. They have conserved structural features and catalytic domains yet show huge variation at different domains resulting in a variety of functions. Myosins are molecules driving various kinds of cellular processes and motility until the level of organisms. These are ATPases that utilize the chemical energy released by ATP hydrolysis to bring about conformational changes leading to a motor function. Myosins are important as they are involved in almost all cellular activities ranging from cell division to transcriptional regulation. They are crucial due to their involvement in many congenital diseases symptomatized by muscular malfunctions, cardiac diseases, deafness, neural and immunological dysfunction, and so on, many of which lead to death at an early age. We present Myosinome, a database of selected myosin classes (myosin II, V, and VI) from five model organisms. This knowledge base provides the sequences, phylogenetic clustering, domain architectures of myosins and molecular models, structural analyses, and relevant literature of their coiled-coil domains. In the current version of Myosinome, information about 71 myosin sequences belonging to three myosin classes (myosin II, V, and VI) in five model organisms ( Homo Sapiens, Mus musculus, D. melanogaster, C. elegans and S. cereviseae) identified using bioinformatics surveys are presented, and several of them are yet to be functionally characterized. As these proteins are involved in congenital diseases, such a database would be useful in short-listing candidates for gene therapy and drug development. The database can be accessed from http://caps.ncbs.res.in/myosinome .

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Simulations of the Myosin II Motor Reveal a Nucleotide-state Sensing Element that Controls the Recovery Stroke

Journal of Molecular Biology ◽

10.1016/j.jmb.2006.06.022 ◽

2006 ◽

Vol 361 (3) ◽

pp. 604-616 ◽

Cited By ~ 29

Author(s):

Sampath Koppole ◽

Jeremy C. Smith ◽

Stefan Fischer

Keyword(s):

Myosin Ii ◽

Sensing Element ◽

Recovery Stroke

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Cooperativity between Two Heads of Dictyostelium Myosin II in in Vitro Motility and ATP Hydrolysis

Biophysical Journal ◽

10.1016/s0006-3495(99)77262-0 ◽

1999 ◽

Vol 76 (2) ◽

pp. 985-992 ◽

Cited By ~ 23

Author(s):

Kohji Ito ◽

Xiong Liu ◽

Eisaku Katayama ◽

Taro Q.P. Uyeda

Keyword(s):

Atp Hydrolysis ◽

Myosin Ii ◽

In Vitro Motility ◽

Dictyostelium Myosin

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The central role of the tail in switching off 10S myosin II activity

The Journal of General Physiology ◽

10.1085/jgp.201912431 ◽

2019 ◽

Vol 151 (9) ◽

pp. 1081-1093 ◽

Cited By ~ 6

Author(s):

Shixin Yang ◽

Kyoung Hwan Lee ◽

John L. Woodhead ◽

Osamu Sato ◽

Mitsuo Ikebe ◽

...

Keyword(s):

Atp Hydrolysis ◽

Myosin Ii ◽

Active Form ◽

Sedimentation Coefficient ◽

Actin Binding ◽

Myosin Filament ◽

Particle Analysis ◽

Compact Structure ◽

Energy Conserving ◽

In Cells

Myosin II is a motor protein with two heads and an extended tail that plays an essential role in cell motility. Its active form is a polymer (myosin filament) that pulls on actin to generate motion. Its inactive form is a monomer with a compact structure (10S sedimentation coefficient), in which the tail is folded and the two heads interact with each other, inhibiting activity. This conformation is thought to function in cells as an energy-conserving form of the molecule suitable for storage as well as transport to sites of filament assembly. The mechanism of inhibition of the compact molecule is not fully understood. We have performed a 3-D reconstruction of negatively stained 10S myosin from smooth muscle in the inhibited state using single-particle analysis. The reconstruction reveals multiple interactions between the tail and the two heads that appear to trap ATP hydrolysis products, block actin binding, hinder head phosphorylation, and prevent filament formation. Blocking these essential features of myosin function could explain the high degree of inhibition of the folded form of myosin thought to underlie its energy-conserving function in cells. The reconstruction also suggests a mechanism for unfolding when myosin is activated by phosphorylation.

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The Structural Coupling between ATPase Activation and Recovery Stroke in the Myosin II Motor

Structure ◽

10.1016/j.str.2007.06.008 ◽

2007 ◽

Vol 15 (7) ◽

pp. 825-837 ◽

Cited By ~ 58

Author(s):

Sampath Koppole ◽

Jeremy C. Smith ◽

Stefan Fischer

Keyword(s):

Myosin Ii ◽

Structural Coupling ◽

Recovery Stroke

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Functional Role of Non-Muscle Myosin II in Microglia: An Updated Review

International Journal of Molecular Sciences ◽

10.3390/ijms22136687 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6687

Author(s):

Chiara Porro ◽

Antonio Pennella ◽

Maria Antonietta Panaro ◽

Teresa Trotta

Keyword(s):

Nervous System ◽

Atp Hydrolysis ◽

Myosin Ii ◽

Cellular Functions ◽

Pathological Conditions ◽

Different Types ◽

The Central Nervous System ◽

Muscle Myosin ◽

Pro Inflammatory Cytokines

Myosins are a remarkable superfamily of actin-based motor proteins that use the energy derived from ATP hydrolysis to translocate actin filaments and to produce force. Myosins are abundant in different types of tissues and involved in a large variety of cellular functions. Several classes of the myosin superfamily are expressed in the nervous system; among them, non-muscle myosin II (NM II) is expressed in both neurons and non-neuronal brain cells, such as astrocytes, oligodendrocytes, endothelial cells, and microglia. In the nervous system, NM II modulates a variety of functions, such as vesicle transport, phagocytosis, cell migration, cell adhesion and morphology, secretion, transcription, and cytokinesis, as well as playing key roles during brain development, inflammation, repair, and myelination functions. In this review, we will provide a brief overview of recent emerging roles of NM II in resting and activated microglia cells, the principal regulators of immune processes in the central nervous system (CNS) in both physiological and pathological conditions. When stimulated, microglial cells react and produce a number of mediators, such as pro-inflammatory cytokines, free radicals, and nitric oxide, that enhance inflammation and contribute to neurodegenerative diseases. Inhibition of NM II could be a new therapeutic target to treat or to prevent CNS diseases.

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Myosin-driven fragmentation of actin filaments triggers contraction of a disordered actin network

10.1101/332684 ◽

2018 ◽

Author(s):

Kyohei Matsuda ◽

Takuya Kobayashi ◽

Mitsuhiro Sugawa ◽

Yurika Koiso ◽

Yoko Y. Toyoshima ◽

...

Keyword(s):

Molecular Mechanism ◽

Actin Filaments ◽

Atp Hydrolysis ◽

Myosin Ii ◽

Network Connectivity ◽

Experimental System ◽

Actin Network ◽

Atp Concentration ◽

Time Required

AbstractThe dynamic cytoskeletal network is responsible for cell shape changes and cell division. The actin-based motor protein myosin II drives the remodeling of a highly disordered actin-based network and enables the network to perform mechanical work such as contraction, migration and adhesion. Myosin II forms bipolar filaments that self-associate via their tail domains. Such myosin minifilaments generate both extensile and compressive forces that pull and push actin filaments, depending on the relative position of myosin and actin filaments in the network. However, it remains unclear how the mechanical properties of myosin II that rely on the energy of ATP hydrolysis spontaneously contract the disordered actin network. Here, we used a minimal in vitro reconstituted experimental system consisting of actin, myosin, and a cross-linking protein, to gain insights into the molecular mechanism by which myosin minifilaments organize disordered actin networks into contractile states. We found that contracted cluster size and time required for the onset of network contraction decreased as ATP concentration decreased. Contraction velocity was negatively correlated with ATP concentrations. Reduction of ATP concentration caused fragmentation of actin filaments by myosin minifilament. We also found that gelsolin, a Ca2+-regulated actin filament-severing protein, induced contraction of a mechanically stable network, implying that fragmentations of actin filaments in the network weaken the intra-network connectivity and trigger contraction. Our findings reveal that the disordered actin network contraction can be controlled by fragmentation of actin filaments, highlighting the molecular mechanism underlying the myosin motor-severing activities, other than the sliding tensile and compressive stress in the disordered actin network.

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Myosin II isoforms in smooth muscle: heterogeneity and function

AJP Cell Physiology ◽

10.1152/ajpcell.00131.2007 ◽

2007 ◽

Vol 293 (2) ◽

pp. C493-C508 ◽

Cited By ~ 63

Author(s):

Thomas J. Eddinger ◽

Daniel P. Meer

Keyword(s):

Smooth Muscle ◽

Conformational Changes ◽

Atp Hydrolysis ◽

Expression Profiles ◽

Myosin Ii ◽

Thick Filament ◽

Actin Binding ◽

Head Region ◽

Organ Systems ◽

Species Specific

Both smooth muscle (SM) and nonmuscle class II myosin molecules are expressed in SM tissues comprising hollow organ systems. Individual SM cells may express one or more of multiple myosin II isoforms that differ in myosin heavy chain (MHC) and myosin light chain (MLC) subunits. Although much has been learned, the expression profiles, organization within contractile filaments, localization within cells, and precise roles in various contractile functions of these different myosin molecules are still not well understood. However, data supporting unique physiological roles for certain isoforms continues to build. Isoform differences located in the S1 head region of the MHC can alter actin binding and rates of ATP hydrolysis. Differences located in the MHC tail can alter the formation, stability, and size of the myosin thick filament. In these distinct ways, both head and tail isoform differences can alter force generation and muscle shortening velocities. The MLCs that are associated with the lever arm of the S1 head can affect the flexibility and range of motion of this domain and possibly the motion of the S2 and motor domains. Phosphorylation of MLC20 has been associated with conformational changes in the S1 and/or S2 fragments regulating enzymatic activity of the entire myosin molecule. A challenge for the future will be delineation of the physiological significance of the heterogeneous expression of these isoforms in developmental, tissue-specific, and species-specific patterns and or the intra- and intercellular heterogeneity of myosin isoform expression in SM cells of a given organ.

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