Location of Repository

Effect of hypertrophic and dilated cardiomyopathies associated mutations in troponin I on cardiac thin filament dynamics

By Sameeh Abdulkareem Al-Sarayreh

Abstract

Troponin I mutations have been linked to genetic hypertrophic and dilated cardiomyopathies. We aimed to understand, at the molecular level, how six HCM mutations (R21C, Q130R, R145G, G203S, and K206Q) and one DCM mutation (A2V) in troponin I affect its structure and function. Circular dichroism, co-sedimentation with actin and ATPase assays demonstrated that these mutations had little or no effect on the folding or the thermal stability of the troponin complex. Isothermal calorimetry, fluorescence spectroscopy, and transient kinetics were used to assess the effect of these mutations on the function of troponin I. We found that: 1) all TnI mutations increased the affinity of the troponin complex for actin in the presence of Ca²+ and increased the Ca²+ affinity of troponin within thin filaments. This suggests an uncoupling between Ca²+ binding and actin binding. 2) The size of the cooperative unit n was not affected by troponin I mutations. 3) A2V, R21C, Q130R, A157V, G203S, and K206Q mutations did not affect the proportion of thin filaments in the blocked state (at low Ca²+). In contrast R145G mutation dramatically reduced the amount of thin filaments switched to the blocked state. This effect was also observed using electron microscopy and helical reconstruction. 4) A2V, R21C, Q130R, R145G, G203S, and K206Q did not affect the observed rate constant of Ca²+ dissociation from troponin and thin filaments. In contrast troponin I A157V showed a decrease in the Ca²+ dissociation rate constant. 5) Finally, we found that calcium alone is sufficient to fully activate the cardiac thin filament while skeletal muscle thin filaments complete activation required both Ca²+ and myosin heads. Overall these results provide insight into the mechanism by which troponin I mutations affect contractility in hypertrophic and dilated cardiomyopathy. These findings could have important clinical consequences

Publisher: University of Leicester
Year: 2011
OAI identifier: oai:lra.le.ac.uk:2381/9693

Suggested articles

Preview

Citations

  1. (2001). (a) Cooperative mechanisms in the activation dependence of the rate of force development in rabbit skinned skeletal muscle fibers,
  2. (2001). (b) Cross-bridge interaction kinetics in rat myocardium are accelerated by strong binding of myosin to the thin filament,
  3. (1980). A fluorescent probe study of Ca2+ binding to the Ca2+-specific sites of cardiac troponin and troponin C,
  4. (2009). A functional and structural study of troponin C mutations related to hypertrophic cardiomyopathy,
  5. (1953). A microcolorimetric method for the determination of inorganic phosphorus,
  6. (2000). A model of troponin-I in complex with troponin-C using hybrid experimental data: the inhibitory region is a beta-hairpin,
  7. (1990). A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation,
  8. (2005). A mutation in the N-terminus of troponin I that is associated with hypertrophic cardiomyopathy affects the Ca(2+)-sensitivity, phosphorylation kinetics and proteolytic susceptibility of troponin,
  9. (1998). A new look at thin filament regulation in vertebrate skeletal muscle,
  10. (2007). Abnormal cardiac response to exercise in a murine model of familial hypertrophic cardiomyopathy,
  11. (1998). Actin mutations in dilated cardiomyopathy, a heritable form of heart failure,
  12. (1999). Actin-myosin interaction,
  13. (1997). Actin-tropomyosin activation of myosin subfragment 1 ATPase and thin filament cooperativity. The role of tropomyosin flexibility and end-to-end interactions,
  14. (1999). Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy,
  15. (1994). Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere,
  16. (1992). Alteration of contractile function and excitation-contraction coupling in dilated cardiomyopathy,
  17. (2000). Altered regulation of cardiac muscle contraction by troponin T mutations that cause familial hypertrophic cardiomyopathy,
  18. (2000). Altered regulatory properties of human cardiac troponin I mutants that cause hypertrophic cardiomyopathy,
  19. (2003). An introduction to cardiovascular physiology. Fourth edition.
  20. (2000). Association of nonsense mutation of dystrophin gene with disruption of sarcoglycan complex in X-linked dilated cardiomyopathy,
  21. (1958). Asymmetrical hypertrophy of the heart in young adults,
  22. (1990). Atomic model of the actin filament,
  23. (1990). Atomic structure of the actin:DNase I complex,
  24. (1999). Binding of cardiac troponin-I147-163 induces a structural opening in human cardiac troponin-C,
  25. (1996). Bisphosphorylation of cardiac troponin I modulates the Ca(2+)-dependent binding of myosin subfragment S1 to reconstituted thin filaments,
  26. (2008). Ca(2+) exchange with troponin C and cardiac muscle dynamics,
  27. (2001). Ca(2+) induces an extended conformation of the inhibitory region of troponin I in cardiac muscle troponin,
  28. (2005). Ca(2+)-regulated structural changes in troponin,
  29. (1992). Ca2+ regulation of mechanical properties of striated muscle. Mechanistic studies using extraction and replacement of regulatory proteins,
  30. (2003). Ca2+-induced conformational transition in the inhibitory and regulatory regions of cardiac troponin I,
  31. (2008). Calcium cycling and signaling in cardiac myocytes,
  32. (1968). Calcium ion and muscle contraction,
  33. (2007). Calcium regulation of troponin and its role in the dynamics of contraction and relaxation,
  34. (2009). Calcium- and myosin-dependent changes in troponin structure during activation of heart muscle,
  35. (1987). Calcium-binding properties of troponin C in detergent-skinned heart muscle fibers,
  36. (2003). Calpain-1-dependent degradation of troponin I mutants found in familial hypertrophic cardiomyopathy,
  37. (1995). Cardiac myosin binding protein-C gene splice acceptor site mutation is associated with familial hypertrophic cardiomyopathy,
  38. (2008). Cardiac thin filament regulation,
  39. (2005). Cardiac troponin I mutations in Australian families with hypertrophic cardiomyopathy: clinical, genetic and functional consequences,
  40. (2008). Cardiac troponin T forms a tetramer in vitro,
  41. (2004). Cardiac troponin T isoforms affect the Ca(2+) sensitivity of force development in the presence of slow skeletal troponin I: insights into the role of troponin T isoforms in the fetal heart,
  42. (2001). Cardiomyopathies: from genetics to the prospect of treatment,
  43. (2004). Cellular and molecular aspects of familial hypertrophic cardiomyopathy caused by mutations in the cardiac troponin I gene,
  44. (1999). Characterization of the cardiac holotroponin complex reconstituted from native cardiac troponin T and recombinant I and C,
  45. (1995). Characterization of the equilibrium between blocked and closed states of muscle thin filaments,
  46. (2000). Clinical features of hypertrophic cardiomyopathy caused by a Lys183 deletion mutation in the cardiac troponin I gene,
  47. (2005). Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counselling,
  48. (1996). Contractile protein mutations and heart disease,
  49. (2006). Controversies in ventricular remodelling,
  50. (1972). Cooperation within actin filament in vertebrate skeletal muscle,
  51. (1999). Cooperativity and switching within the three-state model of muscle regulation,
  52. (1999). Correlation between myofilament response to Ca2+ and altered dynamics of contraction and relaxation in transgenic cardiac cells that express beta-tropomyosin,
  53. (2004). Covalent and noncovalent modification of thin filament action: the essential role of troponin in cardiac muscle regulation,
  54. (2001). Crossbridge and tropomyosin positions observed in native, interacting thick and thin filaments,
  55. (2000). Crystal structure of tropomyosin at 7 Angstroms resolution,
  56. (2000). Deletion in the cardiac troponin I gene in a family from northern Sweden with hypertrophic cardiomyopathy,
  57. (2006). Developmental regulation of intracellular calcium homeostasis in early cardiac myocytes,
  58. Differential protein expression profiling of myocardial tissue in a mouse model of hypertrophic cardiomyopathy,
  59. (2003). Differential regulation of the actomyosin interaction by skeletal and cardiac troponin isoforms,
  60. (2007). Dilated and hypertrophic cardiomyopathy mutations in troponin and alpha-tropomyosin have opposing effects on the calcium affinity of cardiac thin filaments,
  61. (2008). Dimerization of tropomyosins,
  62. (1994). Direct, real-time measurement of rapid inorganic phosphate release using a novel fluorescent probe and its application to actomyosin subfragment 1 ATPase,
  63. (1997). Disparate fluorescence properties of 2-[4'-(iodoacetamido)anilino]-naphthalene-6-sulfonic acid attached to Cys-84 and Cys-35 of troponin C in cardiac muscle troponin,
  64. (1998). Dominant-negative effect of a mutant cardiac troponin T on cardiac structure and function in transgenic mice,
  65. (1982). Dual effects of tropomyosin and troponintropomyosin on actomyosin subfragment 1 ATPase,
  66. (1994). Dynamics of the muscle thin filament regulatory switch: the size of the cooperative unit,
  67. (2000). Effect of Arg145Gly mutation in human cardiac troponin I on the ATPase activity of cardiac myofibrils,
  68. (1980). Effect of dietary fiber on intestinal mucosal sodium-potassium-activated ATPase,
  69. (2001). Effects of phosphorylation and mutation R145G on human cardiac troponin I function,
  70. (2004). Effects of protein kinase C dependent phosphorylation and a familial hypertrophic cardiomyopathy-related mutation of cardiac troponin I on structural transition of troponin C and myofilament activation,
  71. (2002). Effects of T142 phosphorylation and mutation R145G on the interaction of the inhibitory region of human cardiac troponin I with the C-domain of human cardiac troponin C,
  72. (2005). Effects of the mutation R145G in human cardiac troponin I on the kinetics of the contraction-relaxation cycle in isolated cardiac myofibrils,
  73. (2007). Effects of thin and thick filament proteins on calcium binding and exchange with cardiac troponin C,
  74. (1990). Excimer fluorescence of pyrenyliodoacetamide-labeled tropomyosin: a probe of the state of tropomyosin in reconstituted muscle thin filaments,
  75. (1996). Expression and functional assessment of a truncated cardiac troponin T that causes hypertrophic cardiomyopathy. Evidence for a dominant negative action,
  76. (1999). Familial dilated cardiomyopathy: evidence for genetic and phenotypic heterogeneity. Heart Muscle Disease Study Group,
  77. (2003). Familial hypertrophic cardiomyopathy mutations in troponin I (K183D, G203S, K206Q) enhance filament sliding,
  78. (1998). Familial hypertrophic cardiomyopathy: from mutations to functional defects,
  79. (1981). Fluorimetry study of N-(1-pyrenyl)iodoacetamidelabelled F-actin. Local structural change of actin protomer both on polymerization and on binding of heavy meromyosin,
  80. (2007). Folding and regulation in myosins II and V,
  81. (1968). Fractionation of troponin into two distinct proteins,
  82. (2005). Frequency of cardiac troponin I mutations in families with hypertrophic cardiomyopathy in China,
  83. (2002). Functional analysis of a troponin I (R145G) mutation associated with familial hypertrophic cardiomyopathy,
  84. (2001). Functional consequences of the mutations in human cardiac troponin I gene found in familial hypertrophic cardiomyopathy,
  85. (1987). Functional inactivation of genes by dominant negative mutations,
  86. (2005). Gene mutations in adult Japanese patients with dilated cardiomyopathy,
  87. (2000). Homozygous mutation in cardiac troponin T: implications for hypertrophic cardiomyopathy,
  88. (2003). Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy,
  89. (2003). Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy,
  90. (2003). Identification of the genotypes causing hypertrophic cardiomyopathy in northern Sweden,
  91. (1995). In vitro motility analysis of actin-tropomyosin regulation by troponin and calcium. The thin filament is switched as a single cooperative unit,
  92. (2006). Increased Ca2+ affinity of cardiac thin filaments reconstituted with cardiomyopathy-related mutant cardiac troponin I,
  93. (2004). Inherited cardiomyopathies as a troponin disease,
  94. (1992). Inherited idiopathic dilated cardiomyopathy with multiple deletions of mitochondrial DNA,
  95. (1982). Inhibition of actomyosin ATPase activity by troponin-tropomyosin without blocking the binding of myosin to actin,
  96. (2009). Insights into the kinetics of Ca2+-regulated contraction and relaxation from myofibril studies,
  97. (2002). Integration of pathways that signal cardiac growth with modulation of myofilament activity,
  98. (1993). Intracellular calcium homeostasis in cardiac myocytes,
  99. (1983). Intracellular measurements of ion activities,
  100. (2000). Investigation of a truncated cardiac troponin T that causes familial hypertrophic cardiomyopathy: Ca(2+) regulatory properties of reconstituted thin filaments depend on the ratio of mutant to wild-type protein,
  101. (2001). Invited Review: pathophysiology of cardiac muscle contraction and relaxation as a result of alterations in thin filament regulation,
  102. (1987). Isolation and sequence of a cDNA clone for rabbit fast skeletal muscle troponin C. Homology with calmodulin and parvalbumin,
  103. (1992). Isolation, expression, and mutation of a rabbit skeletal muscle cDNA clone for troponin I. The role of the NH2 terminus of fast skeletal muscle troponin I in its biological activity,
  104. (1985). Kinetic studies of calcium binding to regulatory complexes from skeletal muscle,
  105. (1996). Kinetic studies of calcium binding to the regulatory site of troponin C from cardiac muscle,
  106. (1997). Kinetics of nucleoside triphosphate cleavage and phosphate release steps by associated rabbit skeletal actomyosin, measured using a novel fluorescent probe for phosphate,
  107. (1984). Kinetics of the interaction between actin, ADP, and cardiac myosin-S1,
  108. (2008). Lys184 deletion in troponin I impairs relaxation kinetics and induces hypercontractility in murine cardiac myofibrils,
  109. (2001). Macroscopic structure and physiology of the normal and diseased Heart.
  110. (2005). Malignant mutations in hypertrophic cardiomyopathy: fact or fancy?,
  111. (2001). Manipulating the contractile apparatus: genetically defined animal models of cardiovascular disease,
  112. (1971). Mechanism of adenosine triphosphate hydrolysis by actomyosin,
  113. (1986). Mechanism of regulation of cardiac actinmyosin subfragment 1 by troponin-tropomyosin,
  114. (2002). Mechanism of regulation of phosphate dissociation from actomyosin-ADP-Pi by thin filament proteins,
  115. (1996). Mice expressing mutant myosin heavy chains are a model for familial hypertrophic cardiomyopathy,
  116. (2004). Molecular and cellular aspects of troponin cardiomyopathies,
  117. (2006). Molecular insights from a novel cardiac troponin I mouse model of familial hypertrophic cardiomyopathy,
  118. (1997). Molecular motors: structural adaptations to cellular functions,
  119. (1998). Molecular switches in troponin,
  120. (2002). Mutation analysis of the G4.5 gene in patients with isolated left ventricular noncompaction,
  121. (1996). Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle,
  122. (2000). Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy,
  123. (1995). Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy,
  124. (1997). Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy,
  125. (1995). Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy,
  126. (2002). Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy,
  127. (2001). Mutations that alter the surface charge of alpha-tropomyosin are associated with dilated cardiomyopathy,
  128. (2002). Myofilament calcium sensitivity and cardiac disease: insights from troponin I isoforms and mutants,
  129. (2004). Myopathies resulting from mutations in sarcomeric proteins,
  130. (2004). Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy,
  131. (2004). Myosin crossbridge activation of cardiac thin filaments: implications for myocardial function in health and disease,
  132. (2004). NMR and mutagenesis studies on the phosphorylation region of human cardiac troponin I,
  133. (1995). NMR solution structure of calcium-saturated skeletal muscle troponin C,
  134. (2001). Novel cardiac troponin T mutation as a cause of familial dilated cardiomyopathy,
  135. (2001). Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome,
  136. (2004). Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy,
  137. (2001). Overexpression of human cardiac troponin in Escherichia coli: its purification and characterization,
  138. (1994). Overexpression of human cardiac troponin-I and troponin-C in Escherichia coli and their purification and characterisation. Two point mutations allow high-level expression of troponin-I,
  139. (2005). Phenotypic differences between electrocardiographic and echocardiographic determination of hypertrophic cardiomyopathy in genetically affected subjects,
  140. (2002). Phenotypic diversity in hypertrophic cardiomyopathy,
  141. (2003). Phenotyping hypertrophy: eschew obfuscation,
  142. (1995). Phosphorylation of both serine residues in cardiac troponin I is required to decrease the Ca2+ affinity of cardiac troponin
  143. (2003). Phosphorylation of human cardiac troponin I G203S and K206Q linked to familial hypertrophic cardiomyopathy affects actomyosin interaction in different ways,
  144. (1982). Preparation of myosin and its subfragments from rabbit skeletal muscle,
  145. (1982). Preparation of troponin and its subunits,
  146. (2003). Prevalence and spectrum of thin filament mutations in an outpatient referral population with hypertrophic cardiomyopathy,
  147. (1999). Properties of mutant contractile proteins that cause hypertrophic cardiomyopathy,
  148. (2005). Protein kinase cascades in the regulation of cardiac hypertrophy,
  149. (1951). Protein measurement with the Folin phenol reagent,
  150. (1982). Purification of muscle actin,
  151. (1971). Reconstitution of troponin activity from three protein components,
  152. (2000). Regulation of contraction in striated muscle,
  153. (1993). Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament,
  154. (2007). Reviews of translational medicine and genomics in cardiovascular disease: new disease taxonomy and therapeutic implications cardiomyopathies: therapeutics based on molecular phenotype,
  155. (2003). Role of calcium sensitivity modulation in skeletal muscle performance,
  156. (1998). Role of myosin heavy chain composition in kinetics of force development and relaxation in rat myocardium,
  157. (2008). Role of the acidic N' region of cardiac troponin I in regulating myocardial function,
  158. (2002). Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly,
  159. (2005). Sarcomeric protein mutations in dilated cardiomyopathy,
  160. (2005). Sarcomeric proteins and familial hypertrophic cardiomyopathy: linking mutations in structural proteins to complex cardiovascular phenotypes,
  161. (1995). Separation and characterization of the two functional regions of troponin involved in muscle thin filament regulation,
  162. (1975). Separation of subfragment-1 isoenzymes from rabbit skeletal muscle myosin,
  163. (2004). Severe disease expression of cardiac troponin C and T mutations in patients with idiopathic dilated cardiomyopathy,
  164. (1992). Stopped-flow studies of calcium dissociation from calcium-binding-site mutants of Drosophila melanogaster calmodulin,
  165. (1999). Structural analysis of the titin gene in hypertrophic cardiomyopathy: identification of a novel disease gene,
  166. (2004). Structural based insights into the role of troponin in cardiac muscle pathophysiology,
  167. (2001). Structural basis for bending tropomyosin around actin in muscle thin filaments,
  168. (2007). Structural basis for calcium-regulated relaxation of striated muscles at interaction sites of troponin with actin and tropomyosin,
  169. (2009). Structural basis for the activation of muscle contraction by troponin and tropomyosin,
  170. (2008). Structural basis for tropomyosin overlap in thin (actin) filaments and the generation of a molecular swivel by troponin-T,
  171. (1999). Structural mechanism of muscle contraction,
  172. (1973). Structural role of tropomyosin in muscle regulation: analysis of the x-ray diffraction patterns from relaxed and contracting muscles,
  173. (2003). Structure and dynamics of the C-domain of human cardiac troponin C in complex with the inhibitory region of human cardiac troponin I,
  174. (1987). Structure of co-crystals of tropomyosin and troponin,
  175. (2003). Structure of the core domain of human cardiac troponin in the Ca(2+)-saturated form,
  176. (2005). Structure of the mid-region of tropomyosin: bending and binding sites for actin,
  177. (1996). Structure-function analysis of the motor domain of myosin,
  178. (1997). Structures of four Ca2+-bound troponin C at 2.0 Å resolution: further insights into the Ca2+-switch in the calmodulin superfamily,
  179. (1997). Sudden death due to troponin T mutations,
  180. (1989). Sudden death in hypertrophic cardiomyopathy. Assessment of patients at high risk,
  181. (2004). Switching of troponin I: Ca(2+) and myosin-induced activation of heart muscle,
  182. (2006). Synchrotron radiation circular dichroism spectroscopy of proteins and applications in structural and functional genomics,
  183. (1995). The actin fold,
  184. (2002). The crystal structure of the C-terminal fragment of striated-muscle alphatropomyosin reveals a key troponin T recognition site,
  185. (2007). The effect of mutations in alpha-tropomyosin (E40K and E54K) that cause familial dilated cardiomyopathy on the regulatory mechanism of cardiac muscle thin filaments,
  186. (2002). The failing heart,
  187. (2001). The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms,
  188. (2006). The mechanism of smooth muscle caldesmon-tropomyosin inhibition of the elementary steps of the actomyosin ATPase,
  189. (1998). The muscle thin filament as a classical cooperative/allosteric regulatory system,
  190. (2002). The myosin power stroke,
  191. (1975). The primary structure of actin from rabbit skeletal muscle. Completion and analysis of the amino acid sequence,
  192. (1971). The regulation of rabbit skeletal muscle contraction. I. Biochemical studies of the interaction of the tropomyosin-troponin complex with actin and the proteolytic fragments of myosin,
  193. (1994). The regulatory switch of the muscle thin filament: Ca2+ or myosin heads?,
  194. (2005). The role of electrostatics in the interaction of the inhibitory region of troponin I with troponin C,
  195. (2009). The role of the N-terminus of the myosin essential light chain in cardiac muscle contraction,
  196. (2003). The role of tropomyosin in the regulation of myocardial contraction and relaxation,
  197. (2002). The role of troponins in muscle contraction,
  198. (1995). The troponin complex and regulation of muscle contraction,
  199. (2008). The unique functions of cardiac troponin I in the control of cardiac muscle contraction and relaxation,
  200. (1985). The use of actin labelled with N-(1-pyrenyl)iodoacetamide to study the interaction of actin with myosin subfragments and troponin/tropomyosin,
  201. (1980). Theoretical model for the cooperative equilibrium binding of myosin subfragment 1 to the actin-troponin-tropomyosin complex,
  202. (1996). Thin filament-mediated regulation of cardiac contraction,
  203. (1963). Third Component Participating in the Superprecipitation of 'Natural Actomyosin',
  204. (1993). Threedimensional structure of myosin subfragment-1: a molecular motor,
  205. (2000). To the heart of myofibril assembly,
  206. (2000). Transgenic modeling of a cardiac troponin I mutation linked to familial hypertrophic cardiomyopathy,
  207. (2005). Transgenic rabbit model for human troponin I-based hypertrophic cardiomyopathy,
  208. (2000). Tropomyosin and actin isoforms modulate the localization of tropomyosin strands on actin filaments,
  209. (2008). Tropomyosin: function follows structure,
  210. (1982). Troponin and its interactions with tropomyosin. An electron microscope study,
  211. (1999). Troponin I inhibitory peptide (96-115) has an extended conformation when bound to skeletal muscle troponin C,
  212. (1991). Troponin I isoform expression in human heart,
  213. (2010). Troponin T isoforms and posttranscriptional modifications: Evolution, regulation and function,
  214. (1998). Troponin T: genetics, properties and function,
  215. (1984). Troponin-tropomyosin interactions. Fluorescence studies of the binding of troponin, troponin T, and chymotryptic troponin T fragments to specifically labeled tropomyosin,
  216. (2008). Troponin: regulatory function and disorders,
  217. (2002). Two mutations in troponin I that cause hypertrophic cardiomyopathy have contrasting effects on cardiac muscle contractility,
  218. (1998). Use of new methods for construction of tightly regulated arabinose and rhamnose promoter fusions in studies of the Escherichia coli phosphate regulon,
  219. (1990). Use of T7 RNA polymerase to direct expression of cloned genes,
  220. (2006). Using circular dichroism spectra to estimate protein secondary structure,
  221. (2001). Vertebrate tropomyosin: distribution, properties and function,

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.