Genomes and Genes
Summary: Parts of the myosin molecule resulting from cleavage by proteolytic enzymes (PAPAIN; TRYPSIN; or CHYMOTRYPSIN) at well-localized regions. Study of these isolated fragments helps to delineate the functional roles of different parts of myosin. Two of the most common subfragments are myosin S-1 and myosin S-2. S-1 contains the heads of the heavy chains plus the light chains and S-2 contains part of the double-stranded, alpha-helical, heavy chain tail (myosin rod).
- Kovacs M, Thirumurugan K, Knight P, Sellers J. Load-dependent mechanism of nonmuscle myosin 2. Proc Natl Acad Sci U S A. 2007;104:9994-9 pubmed..Whereas forward load accelerates the cycle of interaction with actin, resistive load increases duty ratio to favor tension maintenance by two-headed attachment. ..
- Wendt T, Taylor D, Trybus K, Taylor K. Three-dimensional image reconstruction of dephosphorylated smooth muscle heavy meromyosin reveals asymmetry in the interaction between myosin heads and placement of subfragment 2. Proc Natl Acad Sci U S A. 2001;98:4361-6 pubmed
- Stelzer J, Fitzsimons D, Moss R. Ablation of myosin-binding protein-C accelerates force development in mouse myocardium. Biophys J. 2006;90:4119-27 pubmed..Together, these results support the idea that cMyBP-C normally acts to constrain the interaction between myosin and actin, which in turn limits steady-state force development and the kinetics of cross-bridge interaction. ..
- Sundberg M, Bunk R, Albet Torres N, Kvennefors A, Persson F, Montelius L, et al. Actin filament guidance on a chip: toward high-throughput assays and lab-on-a-chip applications. Langmuir. 2006;22:7286-95 pubmed..The results are discussed in relation to lab-on-a-chip applications and nanotechnology-assisted assays of actomyosin function. ..
- Trybus K, Freyzon Y, Faust L, Sweeney H. Spare the rod, spoil the regulation: necessity for a myosin rod. Proc Natl Acad Sci U S A. 1997;94:48-52 pubmed..Expressed smooth muscle myosin subfragments with as many as 100 amino acids of the coiled-coil rod sequence did not dimerize and were active ..
- Rayment I, Rypniewski W, Schmidt Bäse K, Smith R, Tomchick D, Benning M, et al. Three-dimensional structure of myosin subfragment-1: a molecular motor. Science. 1993;261:50-8 pubmed..This structure of a molecular motor was determined by single crystal x-ray diffraction. The data provide a structural framework for understanding the molecular basis of motility. ..
- Kawai M, Kawaguchi K, Saito M, Ishiwata S. Temperature change does not affect force between single actin filaments and HMM from rabbit muscles. Biophys J. 2000;78:3112-9 pubmed..These results indicate that the amount of force each cross-bridge generates is fixed, and it does not change with temperature. We found that the above generalization was not modified in the presence of 1 mM MgADP or 8 mM phosphate. ..
- Klinth J, Arner A, Mansson A. Cardiotonic bipyridine amrinone slows myosin-induced actin filament sliding at saturating [MgATP]. J Muscle Res Cell Motil. 2003;24:15-32 pubmed..Such a well-defined effect on the myosin cross-bridge cycle makes the drug a potentially useful pharmacological tool for further studies of myosin function both in vitro and in the ordered filament array of a living muscle fiber. ..
- Swartz D, Moss R, Greaser M. Calcium alone does not fully activate the thin filament for S1 binding to rigor myofibrils. Biophys J. 1996;71:1891-904 pubmed..These results suggest that calcium alone does not fully activate the thin filament for rigor S1 binding and that, even at high calcium, the thin filament is not activated along its entire length. ..
- Molloy J, Burns J, Kendrick Jones J, Tregear R, White D. Movement and force produced by a single myosin head. Nature. 1995;378:209-12 pubmed..We measure the average force generated by S1 or HMM to be at least 1.7 pN under isometric conditions. ..
- Nyitrai M, Rossi R, Adamek N, Pellegrino M, Bottinelli R, Geeves M. What limits the velocity of fast-skeletal muscle contraction in mammals?. J Mol Biol. 2006;355:432-42 pubmed..Extrapolating our data to 37 degrees C suggests that at physiological temperature the rate of ADP dissociation may limit Vo for both isoforms. ..
- Balaz M, Sundberg M, Persson M, Kvassman J, Mansson A. Effects of surface adsorption on catalytic activity of heavy meromyosin studied using a fluorescent ATP analogue. Biochemistry. 2007;46:7233-51 pubmed..Furthermore, we propose a novel TIRF microscopy method to accurately determine the surface density of catalytically active myosin motors. ..
- Stelzer J, Patel J, Olsson M, Fitzsimons D, Leinwand L, Moss R. Expression of cardiac troponin T with COOH-terminal truncation accelerates cross-bridge interaction kinetics in mouse myocardium. Am J Physiol Heart Circ Physiol. 2004;287:H1756-61 pubmed..Although these mechanisms would not be expected to depress systolic function per se in cTnT(trunc) hearts, they would account for slowed rates of myocardial relaxation during early diastole. ..
- Berger C, Fagnant P, Heizmann S, Trybus K, Geeves M. ADP binding induces an asymmetry between the heads of unphosphorylated myosin. J Biol Chem. 2001;276:23240-5 pubmed..A model that incorporates strain between the two heads is proposed to explain the data, which have implications for how one head of a motor protein can gate the response of the other. ..
- Fitzsimons D, Patel J, Campbell K, Moss R. Cooperative mechanisms in the activation dependence of the rate of force development in rabbit skinned skeletal muscle fibers. J Gen Physiol. 2001;117:133-48 pubmed
- Schoffstall B, Brunet N, Williams S, Miller V, Barnes A, Wang F, et al. Ca2+ sensitivity of regulated cardiac thin filament sliding does not depend on myosin isoform. J Physiol. 2006;577:935-44 pubmed..Our motility results suggest that the cellular changes in isoform expression that result in regulation of myosin kinetics can occur independently of changes that influence thin filament Ca(2+) sensitivity. ..
- Persson M, Gullberg M, Tolf C, Lindberg A, Mansson A, Kocer A. Transportation of nanoscale cargoes by myosin propelled actin filaments. PLoS ONE. 2013;8:e55931 pubmed publisher..The attachment of quantum dots via CapZ, without appreciable modulation of actomyosin function, is useful in fundamental studies as exemplified here by tracking with nanometer accuracy. ..
- Cheung A, Dantzig J, Hollingworth S, Baylor S, Goldman Y, Mitchison T, et al. A small-molecule inhibitor of skeletal muscle myosin II. Nat Cell Biol. 2002;4:83-8 pubmed..The isolation of BTS and the recently discovered Eg5 kinesin inhibitor, monastrol, suggests that motor proteins may be potential targets for therapeutic applications. ..
- Volkmann N, Ouyang G, Trybus K, Derosier D, Lowey S, Hanein D. Myosin isoforms show unique conformations in the actin-bound state. Proc Natl Acad Sci U S A. 2003;100:3227-32 pubmed
- Calaghan S, Trinick J, Knight P, White E. A role for C-protein in the regulation of contraction and intracellular Ca2+ in intact rat ventricular myocytes. J Physiol. 2000;528 Pt 1:151-6 pubmed
- Iwabuchi S, Takahashi T, Hatori K. Transport of actin-decorated liposomes along myosin molecules in vitro. Biochem Biophys Res Commun. 2012;422:164-8 pubmed publisher..These data show that the actomyosin system was successfully integrated into the liposomes and possesses the ability to actively transport useful agents enclosed within the liposomes. ..
- Holmes K, Angert I, Kull F, Jahn W, Schröder R. Electron cryo-microscopy shows how strong binding of myosin to actin releases nucleotide. Nature. 2003;425:423-7 pubmed..The closing of the actin-binding cleft when actin binds is structurally coupled to the opening of the nucleotide-binding pocket. ..
- Razumova M, Shaffer J, Tu A, Flint G, Regnier M, Harris S. Effects of the N-terminal domains of myosin binding protein-C in an in vitro motility assay: Evidence for long-lived cross-bridges. J Biol Chem. 2006;281:35846-54 pubmed..The results suggest that N-terminal domains of MyBP-C slow cross-bridge cycling kinetics by reducing rates of cross-bridge detachment. ..
- Siemankowski R, Wiseman M, White H. ADP dissociation from actomyosin subfragment 1 is sufficiently slow to limit the unloaded shortening velocity in vertebrate muscle. Proc Natl Acad Sci U S A. 1985;82:658-62 pubmed..iii) Variation with muscle type of the rate constant for ADP dissociation may be a general phylogenetic mechanism for regulating shortening velocity. ..
- Albet Torres N, O Mahony J, Charlton C, Balaz M, Lisboa P, Aastrup T, et al. Mode of heavy meromyosin adsorption and motor function correlated with surface hydrophobicity and charge. Langmuir. 2007;23:11147-56 pubmed..The results are compared to previous studies of the microtubule-kinesin system and are also discussed in relation to fundamental studies of actomyosin and nanotechnological developments and applications. ..
- Cecchini M, Houdusse A, Karplus M. Allosteric communication in myosin V: from small conformational changes to large directed movements. PLoS Comput Biol. 2008;4:e1000129 pubmed publisher..The mechanism of the uncoupling of the converter from the motor head, an essential part of the transition, is elucidated. The origin of the partial untwisting of the central beta-sheet in the rigor to post-rigor transition is described. ..
- Gordon A, LaMadrid M, Chen Y, Luo Z, Chase P. Calcium regulation of skeletal muscle thin filament motility in vitro. Biophys J. 1997;72:1295-307 pubmed..Comparison of motility results with the force-pCa relationship in fibers suggests that relatively few cross-bridges are needed to make filaments move, but many have to be cycling to make the regulated filament move at maximum speed. ..
- Shakirova L, Mikhailova V, Siletskaya E, Timofeev V, Levitsky D. Nucleotide-induced and actin-induced structural changes in SH1-SH2-modified myosin subfragment 1. J Muscle Res Cell Motil. 2007;28:67-78 pubmed
- Lieleg O, Claessens M, Luan Y, Bausch A. Transient binding and dissipation in cross-linked actin networks. Phys Rev Lett. 2008;101:108101 pubmed..We reproduce the measured frequency response by a semiphenomenological model that is predicated on microscopic unbinding events. ..
- Vikhorev P, Vikhoreva N, Sundberg M, Balaz M, Albet Torres N, Bunk R, et al. Diffusion dynamics of motor-driven transport: gradient production and self-organization of surfaces. Langmuir. 2008;24:13509-17 pubmed publisher..This forms the basis for secondary chemical and topographical gradients with implications for cell biological studies and biosensing. ..
- Shaffer J, Razumova M, Tu A, Regnier M, Harris S. Myosin S2 is not required for effects of myosin binding protein-C on motility. FEBS Lett. 2007;581:1501-4 pubmed..Results demonstrate that effects of C1C2 are comparable in both systems and suggest that the MyBP-C motif affects motility through direct interactions with actin and/or myosin S1. ..
- Markov D, Pivovarova A, Chernik I, Gusev N, Levitsky D. Small heat shock protein Hsp27 protects myosin S1 from heat-induced aggregation, but not from thermal denaturation and ATPase inactivation. FEBS Lett. 2008;582:1407-12 pubmed publisher..However, Hsp27 was unable to prevent thermal unfolding of myosin heads and to maintain their ATPase activity under heat-shock conditions. ..
- Mansson A, Balaz M, Albet Torres N, Rosengren K. In vitro assays of molecular motors--impact of motor-surface interactions. Front Biosci. 2008;13:5732-54 pubmed..g. myosin filaments) will be considered. Finally, this review will consider the implications for further developments of motor-powered lab-on-a-chip devices. ..
- Tanaka Takiguchi Y, Kakei T, Tanimura A, Takagi A, Honda M, Hotani H, et al. The elongation and contraction of actin bundles are induced by double-headed myosins in a motor concentration-dependent manner. J Mol Biol. 2004;341:467-76 pubmed..The double-headed structure of myosins may also be important for generating tension or elongation in actin bundles or gels, and for organizing polarity-sorted actin networks, not just for improving their motor processivity or activity. ..
- Fitzsimons D, Patel J, Moss R. Cross-bridge interaction kinetics in rat myocardium are accelerated by strong binding of myosin to the thin filament. J Physiol. 2001;530:263-72 pubmed
- Dominguez R, Freyzon Y, Trybus K, Cohen C. Crystal structure of a vertebrate smooth muscle myosin motor domain and its complex with the essential light chain: visualization of the pre-power stroke state. Cell. 1998;94:559-71 pubmed..A comparison of the lever arm positions in MDE-AIF4- and in nucleotide-free skeletal S1 shows that a potential displacement of approximately 10 nm can be achieved during the power stroke. ..
- Harris S, Rostkova E, Gautel M, Moss R. Binding of myosin binding protein-C to myosin subfragment S2 affects contractility independent of a tether mechanism. Circ Res. 2004;95:930-6 pubmed
- Gourinath S, Himmel D, Brown J, Reshetnikova L, Szent Györgyi A, Cohen C. Crystal structure of scallop Myosin s1 in the pre-power stroke state to 2.6 a resolution: flexibility and function in the head. Structure. 2003;11:1621-7 pubmed..The agreement between structural and solution studies reinforces the view that the unwinding of the SH1 helix is a part of the cross-bridge cycle in many myosins. ..
- Burgess S, Yu S, Walker M, Hawkins R, Chalovich J, Knight P. Structures of smooth muscle myosin and heavy meromyosin in the folded, shutdown state. J Mol Biol. 2007;372:1165-78 pubmed..The folded tail does not modify the compact head arrangement but stabilises it, indicating a structural mechanism for the very low ATPase activity of the folded molecule. ..
- Criddle A, Geeves M, Jeffries T. The use of actin labelled with N-(1-pyrenyl)iodoacetamide to study the interaction of actin with myosin subfragments and troponin/tropomyosin. Biochem J. 1985;232:343-9 pubmed..to Cys-374 of actin has been shown to be a useful probe for monitoring the interaction of actin with myosin subfragments [Kouyama & Mihashi (1981) Eur. J. Biochem. 114, 33-38]...
- Homsher E, Nili M, Chen I, Tobacman L. Regulatory proteins alter nucleotide binding to acto-myosin of sliding filaments in motility assays. Biophys J. 2003;85:1046-52 pubmed..It is hypothesized that structural changes in the actin portion of the acto-myosin interface are induced by regulatory protein binding to actin. ..
- Shaw M, Ostap E, Goldman Y. Mechanism of inhibition of skeletal muscle actomyosin by N-benzyl-p-toluenesulfonamide. Biochemistry. 2003;42:6128-35 pubmed..ADP.P(i) and S1.ADP for actin. ..
- Markov D, Zubov E, Nikolaeva O, Kurganov B, Levitsky D. Thermal denaturation and aggregation of myosin subfragment 1 isoforms with different essential light chains. Int J Mol Sci. 2010;11:4194-226 pubmed publisher..Under these conditions kinetics of this process was independent of protein concentration, and the aggregation rate was limited by irreversible denaturation of the S1 motor domain. ..
- Margossian S, Lowey S. Interaction of myosin subfragments with F-actin. Biochemistry. 1978;17:5431-9 pubmed..The small difference in binding energy between HMM and S1 suggests that either only one head can bind strongly to actin at a time or that free energy is lost during the sterically unfavorable attachment of the two heads to actin. ..
- Alcala D, Haldeman B, Brizendine R, Krenc A, Baker J, Rock R, et al. Myosin light chain kinase steady-state kinetics: comparison of smooth muscle myosin II and nonmuscle myosin IIB as substrates. Cell Biochem Funct. 2016;34:469-474 pubmed publisher..We show that the MLCK prefers smooth muscle myosin by a significant factor. These data suggest that nonmuscle myosin is phosphorylated more slowly than smooth muscle myosin during a contraction cycle. ..
- Reshetnyak Y, Andreev O. The interdomain motions in myosin subfragment 1. Biophys Chem. 2001;94:41-6 pubmed..These findings led to the suggestion that a release of the products of ATP hydrolysis and power stroke might be associated with movement of light chain-binding domain towards the N-terminal domain of S1. ..
- Labbe J, Chamayou S, Benyamin Y. Interaction of 75-106 actin peptide with myosin subfragment-1 and its trypsin modified derivative. Biochim Biophys Acta. 1999;1427:105-11 pubmed..4x10(-6) M, this fragment did not bind to the trypsin S-1 derivative. We concluded that the actin 85-95 sequence should be a potential binding site to S-1 depending of the conformational state of the intact 70 kDa segment of S-1. ..
- Maruta S, Mizukura Y, Chaen S. Interaction of a new fluorescent ATP analogue with skeletal muscle myosin subfragment-1. J Biochem. 2002;131:905-11 pubmed..ADP.BeF(n) or AlF(4)(-) reported previously by our group. Our novel ATP analogue seems to be applicable to kinetic studies on myosin. ..
- Moraczewska J, Gruszczynska Biegala J, Redowicz M, Khaitlina S, Strzelecka Golaszewska H. The DNase-I binding loop of actin may play a role in the regulation of actin-myosin interaction by tropomyosin/troponin. J Biol Chem. 2004;279:31197-204 pubmed..Our results point to a possible role of the N-terminal part of loop 38-52 of actin in communication between tropomyosin and myosin through changes in actin structure. ..
- Reed Z, Park J. Thermophysical characterization of tilapia myosin and its subfragments. J Food Sci. 2011;76:C1050-5 pubmed publisher..The results also showed that the thermo stability of the myosin and its subfragments were greatly influenced by fish habitat temperature. ..
- Chen L, Blanc E, Chapman M, Taylor K. Real space refinement of acto-myosin structures from sectioned muscle. J Struct Biol. 2001;133:221-32 pubmed..The methodology seems to be well suited to the derivation of stereochemically reasonable atomic models that are consistent with experimentally determined 3-D reconstructions computed from electron micrographs. ..
- Stepkowski D, Efimova N, Paczyņska A, Moczarska A, Nieznanska H, Kakol I. The possible role of myosin A1 light chain in the weakening of actin-myosin interaction. Biochim Biophys Acta. 1997;1340:105-14 pubmed..Such an effect requires a structural minimum that is present in HMM but not in subfragment-1. Implications of such a role for the A1 N-terminus in the myosin-actin interaction are discussed. ..
- Hayley M, Chevaldina T, Mudalige W, Jackman D, Dobbin A, Heeley D. Shark skeletal muscle tropomyosin is a phosphoprotein. J Muscle Res Cell Motil. 2008;29:101-7 pubmed publisher..The difference is attributable chiefly to a change in Vmax. Skeletal muscle tropomyosin is concluded to be phosphorylated in cartilaginous fishes as well as some teleosts. ..