ライフサイエンスコーパス: thin filament

1 ng the whole approximately 1 mum length of a thin filament.

2 neighboring molecules 400 nm along the actin thin filament.

3 ust rapidly attach and detach from the actin thin filament.

4 that are associated with the skeletal muscle thin filament.

5 x and large macromolecular assembly like the thin filament.

6 tions, forming a continuous strand along the thin filament.

7 el, calcium modulates myosin's access to the thin filament.

8 d to laterally activate a regulatory unit of thin filament.

9 ssumes a single myosin head can activate the thin filament.

10 wo myosin heads are required to activate the thin filament.

11 y of cNTnC within the context of the cardiac thin filament.

12 e azimuthal motion of tropomyosin around the thin filament.

13 ve cardiac myosin-binding protein C with the thin filament.

14 is thought to be a disease of the sarcomere thin filament.

15 form cross-bridges with the actin-containing thin filament.

16 T45-74, attenuated maximal activation of the thin filament.

17 n gene encodes a component of the sarcomeric thin filament.

18 - and Ca(2+)-saturated states of the cardiac thin filament.

19 orter fragments were unable to sensitize the thin filament.

20 ther the myosin head region and/or the actin thin filament.

21 the thick filaments and on troponin C in the thin filaments.

22 ganized, contain rod bodies, and have longer thin filaments.

23 lity by binding to and moving along actin of thin filaments.

24 protein localized at the pointed end of the thin filaments.

25 mere length relations, indicative of shorter thin filaments.

26 uted WT and cardiac troponin T R92L and R92W thin filaments.

27 r potential interactions with both thick and thin filaments.

28 ed increased mass/ordering in both thick and thin filaments.

29 nding stiffness of F-actin and reconstructed thin filaments.

30 le the N-terminus extends toward neighboring thin filaments.

31 an increase in the bending stiffness of the thin filaments.

32 olecules of myosin binding to and activating thin filaments.

33 esulted in shortening and disorganization of thin filaments.

34 ned by an interaction between MyBP-C and the thin filaments.

35 n, showing that C1mC2 directly activates the thin filaments.

36 ted by an interaction between MyBP-C and the thin filaments.

37 l effects of N-terminal fragments binding to thin filaments.

38 tropomyosin to an inhibitory position along thin filaments.

39 filament pointed ends and fails to elongate thin filaments.

40 y of nebulin being localized properly in the thin filaments.

41 h the Ca(2+)-dependent regulation of cardiac thin filaments.

42 fragment 1: evidence for three states of the thin filament."

43 ents are caused by structural changes in the thin filament, a sarcomeric microstructure.

44 (K206I), we tested the Ca(2+) dependence of thin filament-activated myosin-S1-ATPase activity in a r

45 known about how it modulates the kinetics of thin filament activation and myofibril relaxation as Ca(

46 mutations (S23D/S24D-cTnI), directly affects thin filament activation and myofilament relaxation kine

47 n, via PKA phosphorylation of cTnI, may slow thin filament activation and result in increased myofila

48 omyopathy, A277V, will alter Tpm binding and thin filament activation by altering the overlap structu

49 ition, and that this movement corresponds to thin filament activation in the motility assay.

50 Three thin filament activation states possessing differential

51 dependent change in [Ca(2+) ]-sensitivity of thin filament activation.

52 ick filaments, controlled by calcium through thin filament activation.

53 via increasing cross-bridge contributions to thin-filament activation as cross-bridge kinetics slow a

54 itment of neighboring cross-bridges, because thin-filament activation is not already saturated.

55 cale myofilament model that can describe the thin-filament activation process during contraction.

56 During cardiac thin-filament activation, the N-domain of cardiac tropon

57 pomyosin movement over actin subunits during thin-filament activation, thus reducing both the fractio

58 We focus here on the modulation of thin filament activity by cardiac troponin I phosphoryla

59 This suggests that cMyBP-C might modulate thin filament activity by interfering with tropomyosin r

60 sults suggest that cMyBP-C may both modulate thin filament activity, by physically displacing tropomy

61 muscle contraction involves sliding of actin thin filaments along myosin thick filaments, controlled

62 erstood, but might involve the length of the thin filament, an important determinant of force generat

63 Troponin T (TnT) is the thin-filament-anchoring subunit of troponin.

64 eak-binding mode to search for access to the thin filament and a tight-binding mode to sensitize the

65 increases the Ca(2+)-binding affinity of the thin filament and elicits changes in Ca(2+) homeostasis

66 new era has arrived for investigation of the thin filament and for functional understandings that inc

67 n of tropomyosin's reconfiguration along the thin filament and key for the cooperative switching betw

68 in the C-zone, MyBP-C Ca(2+) sensitizes the thin filament and slows thin filament velocity.

69 lymerization, HSPB7 KO mice had longer actin/thin filaments and developed abnormal actin filament bun

70 gments (Cy3-C0C1 and Cy3-C0C1f) bound to the thin filaments and displayed modes of motion on the thin

71 inct structural changes of troponin C in the thin filaments and myosin regulatory light chain in the

72 used fluorescent probes on troponin C in the thin filaments and on myosin regulatory light chain in t

73 deno-associated viral transduction elongates thin filaments and rescues structural and functional def

74 region of MyBP-C stabilizes the ON state of thin filaments and the OFF state of thick filaments and

75 raction studies with isolated cardiac native thin filaments and the S2 domain of cardiac myosin to sh

76 Adult HCM patients (age >18 years), 80 with thin-filament and 150 with thick-filament mutations, wer

77 binds to actin - a major constituent of the thin filament - and that mutations in KBTBD13 cause stru

78 myosin molecule to a single regulated actin thin filament, and separately determined the distance ov

79 calcium to troponin in the actin-containing thin filaments, and a structural change in the thin fila

80 tin (F-actin) is the major protein of muscle thin filaments, and actin microfilaments are the main co

81 s of the regulatory protein, tropomyosin, on thin filaments, and conversely tropomyosin affects myosi

82 In skeletal muscle, thick and thin filaments are arranged in a myofibrillar lattice.

83 Improper lengths of actin-thin filaments are associated with altered contractile a

84 n cytoskeleton and the attached Z-band-bound thin filaments are degraded after ubiquitination by the

85 perative structural changes in the thick and thin filaments are fundamental to the physiological regu

86 the thick filaments that do not overlap with thin filaments are highly disordered during isometric co

87 Vertebrate striated muscle thin filaments are thought to be thermodynamically activ

88 yosin molecules are required to activate the thin filament arises from an assumption, made during dat

89 Actin-based thin filament arrays constitute a fundamental core compo

90 for studying the assembly and maturation of thin-filament arrays in a skeletal muscle model system.

91 stinct phases in the dynamic construction of thin-filament arrays.

92 NM is thought to be a disease of sarcomeric thin filaments as six of eight known genes whose mutatio

93 The Z-disc is a critical anchoring point for thin filaments as they slide during muscle contraction.

94 pomodulin family of proteins, is critical in thin filament assembly and maintenance; however, its rol

95 t layers, suggesting that the major place of thin filament assembly is an M-line-centered narrow doma

96 licated in the regulation of striated muscle thin filament assembly; its physiological function has y

97 nd tropomyosin-binding protein that controls thin-filament assembly, stability, and lengths.

98 did not displace tropomyosin or activate the thin filament at low Ca(2+) but slowed thin filament sli

99 eve this is by binding directly to the actin-thin filament at low calcium levels to enhance the movem

100 n a slower and less complete deactivation of thin filaments at the end of contractions.

101 on tuning cMyBP-C's calcium-sensitization of thin filaments at the low calcium levels between contrac

102 nin I in a network involving the ends of the thin filaments at the Z-disk and the M-band regions.

103 d azimuthal slew of the lever arm around the thin filament axis, which was not predicted from known c

104 resulting in their repositioning toward the thin filament before activation.

105 rated that these fragments diffuse along the thin filament before statically binding, suggesting a me

106 SL, possibly through reduced availability of thin filament binding sites (cTnI) or altered crossbridg

107 ulate thin filament lengths by competing for thin filament binding.

108 Dynamic imaging of thin filament-bound Cy3-C0C3 molecules demonstrated that

109 d by calcium binding to the actin-containing thin filaments but modulated by structural changes in th

110 proaches to track myosin head binding to the thin filament, but is absent in the regulatory head.

111 rganization on native relaxed cardiac muscle thin filaments by applying single particle reconstructio

112 discovered that Lmod2 functions to elongate thin filaments by promoting actin assembly and dynamics

113 ermine each MyBP-C isoform's contribution to thin filament Ca(2+) sensitization and slowing in the C-

114 Absence of components of the sarcomeric thin filaments causes nemaline myopathy, a lethal congen

115 n filaments in the I-band, where nebulin and thin filaments coalign.

116 myosin fails to localize properly within the thin filament compartment and its expression alters sarc

117 onal approaches to deduce global dynamics of thin filament components by energy landscape determinati

118 dependent interactions of myosin motors with thin filaments composed of the proteins actin, troponin,

119 The striated muscle thin filament comprises actin, tropomyosin, and troponin

120 Complete description of thin filament conformational transitions accompanying mu

121 itioning requires associations between other thin filament constituents.

122 force-generating cross-bridges and shortened thin filaments contribute to the force deficit.

123 ropomyosin decreased calcium sensitivity and thin filament cooperativity.

124 elta) + Tm(H276N) fibers, whereas diminished thin-filament cooperativity attenuated tension in McTnT(

125 binding and dissociation within the cardiac thin filament (CTF) is a fundamental regulator of normal

126 d the 3-state model of activation of cardiac thin filaments (cTFs) isolated as a complex and deposite

127 relaxation, related to myosin detachment and thin filament deactivation rates, decreased with gestati

128 ied variant-specific pathophysiology using a thin filament-directed calcium reporter to monitor chang

129 (2016) atomistic model of the thin filament displays a paucity of salt bridges and hyd

130 in-S1 heads that can interact with the actin thin filament during transition from the weakly to the s

131 ld-type or Tmod4(-/-) muscle fibers leads to thin filament elongation by approximately 15%.

132 Two missense variants in thin filament encoding genes were commonly seen in Singa

133 the C0C3 N-terminal cMyBP-C fragment to the thin filament enhanced myosin association at low calcium

134 ativity of calcium response of the regulated thin filaments even in the absence of myosin heads.

135 K210, respectively), were examined using the thin-filament extraction/reconstitution technique.

136 , tropomyosin cable wrapping around actin of thin filaments features both head-to-tail polymeric inte

137 anding of the troponin complex on the muscle thin filament, focusing on conformational changes in fle

138 ds may remain in an activated state near the thin filaments following relaxation, accounting for the

139 in a second to yield a pathogenic change in thin filament function that results in mutation-specific

140 omyosin to F-actin is required for effective thin filament function.

141 tin mimic ones that occur in early stages of thin-filament generation, as if the mutants are recapitu

142 thogenic sarcomeric variant, particularly in thin filament genes (HR, 1.5 [95% CI, 1.0-2.1] and 2.5 [

143 ever, recent discoveries of mutations in non-thin filament genes has called this model in question.

144 This suggests that the thin filament has the potential to be turned fully on or

145 ach, the cooperative binding of myosin along thin filaments has been quantified.

146 skeletal muscle in which both the thick and thin filaments have a regulatory function.

147 iphasic LV filling is particularly common in thin-filament HCM, reflecting profound diastolic dysfunc

148 e domains needed to bind specifically to the thin filament in order for the cMyBP-C N terminus to mod

149 ), and affinity measurements of cTnC for the thin filament in reconstituted papillary muscles to prov

150 ts and interact with surrounding actin-based thin filaments in a dense, near-crystalline hexagonal la

151 myosin molecules binding to suspended actin-thin filaments in a fluorescence-based single-molecule m

152 ordinates the regulatory states of thick and thin filaments in both physiological and potentially pat

153 We present a model of Ca-regulated thin filaments in cardiac muscle where tropomyosin is tr

154 its localization at the pointed ends of the thin filaments in cardiomyocytes.

155 uns and pauses of individual skeletal muscle thin filaments in cycling myosin motility assays.

156 the structure and organization of thick and thin filaments in muscle and the interaction of myosin w

157 Confocal microscopy confirmed shorter thin filaments in muscle fibers of these patients.

158 ting the stabilization and function of actin thin filaments in muscle.

159 between actin and tropomyosin on myosin-free thin filaments in relaxed muscle, thus restructuring the

160 essential for the organization of sarcomeric thin filaments in skeletal muscle.

161 sarcomeres to control the precise length of thin filaments in the contractile apparatus.

162 pel myosin thick filaments relative to actin thin filaments in the fiber.

163 of Lmod2 in mice results in abnormally short thin filaments in the heart.

164 th in sarcomeres, potentially by stabilizing thin filaments in the I-band, where nebulin and thin fil

165 n occurs when myosin thick filaments bind to thin filaments in the sarcomere and generate pulling for

166 f muscle fibers as well as the length of the thin filaments, in muscle fibers from 51 patients with t

167 ges in myofilament spacing (d(1,0)) or thick-thin filament interaction.

168 mutation-induced alterations in tropomyosin-thin filament interactions underlie the altered regulato

169 available to interact with actin-containing thin filaments is controlled by the stress in the myosin

170 ller Z-discs in their core, whilst the thick/thin filament lattice can form peripherally without a Z-

171 ever, the precise role of nebulin in setting thin filament length and its other functions in regulati

172 t shock protein in directly modulating actin thin filament length in cardiac muscle by binding monome

173 Nebulin sets actin thin filament length in sarcomeres, potentially by stabi

174 dentify Tmod1 as the key direct regulator of thin filament length in skeletal muscle, in both adult m

175 disappears from soleus muscle, resulting in thin filament length increases of approximately 10 and a

176 lts implicate Tmod proteolysis and resultant thin filament length misspecification as novel mechanism

177 ing questions about the role of leiomodin in thin filament length regulation and maintenance.

178 whereas Tmod4 appears to be dispensable for thin filament length regulation.

179 uggest that pointed-end assembly and Tmod1's thin filament length regulatory function are regulated b

180 distinct sites in the sarcomere and controls thin filament length with just two nebulin repeats.

181 d that abnormal actin bundles, not elongated thin filament length, were the cause of embryonic lethal

182 sm where leiomodin and tropomodulin regulate thin filament lengths by competing for thin filament bin

183 than total sarcomeric Tmod levels, controls thin filament lengths in mouse skeletal muscle, whereas

184 and Lmod3 to control myofibril organization, thin filament lengths, and actomyosin crossbridge format

185 nerate Tmod4(-/-) mice, which exhibit normal thin filament lengths, myofibril organization, and skele

186 in filament myopathy patients with shortened thin filament lengths.

187 , resulting in approximately 11% increase in thin filament lengths.

188 omodulin and leiomodin, controls the uniform thin-filament lengths crucial for normal sarcomere struc

189 ted with actin-subunits along the surface of thin filaments, makes electrostatic interactions with cl

190 emperature because cooperative activation of thin filaments may already be saturated.

191 provides a structural correlate to evaluate thin-filament mechanics, self-assembly mechanisms, and t

192 l muscle cells that, although the well-known thin-filament mechanism is sufficient for regulation of

193 This calcium/thin filament mediated pathway provides the "START" sign

194 es that acts independently of the well-known thin filament-mediated calcium signalling pathway.

195 m levels necessary to maximally activate the thin filament mitigated the structural effects of phosph

196 ed computational work aiming to improve TnT1-thin filament models by employing unbiased docking metho

197 l, using homogenization theory and atomistic thin filament models from the Protein Data Bank.

198 operative activation observed with regulated thin filament motility indicates that increased overlap

199 actin via its N-terminal domains, modulating thin filament motility.

200 anization of troponin and tropomyosin on the thin filament must be determined.

201 In adult HCM patients, thin-filament mutations are associated with increased li

202 cohort of patients with HCM associated with thin-filament mutations compared with thick-filament HCM

203 pared with thick-filament HCM, patients with thin-filament mutations showed: 1) milder and atypically

204 hypertrophic cardiomyopathy (HCM) caused by thin-filament mutations.

205 Thin filament myopathies are among the most common nondy

206 ents, in muscle fibers from 51 patients with thin filament myopathy caused by mutations in NEB, ACTA1

207 he development of therapeutic strategies for thin filament myopathy patients with shortened thin fila

208 eb knockout mouse model, which recapitulates thin filament myopathy, revealed a compensatory mechanis

209 ensitivity observed in Ca(2+) binding to the thin filament, myosin S1-ADP binding to the thin filamen

210 ecular mechanism of muscle activation in the thin filament-myosin head complex under physiological co

211 ructural changes separately in the thick and thin filaments of rat cardiac muscle, to elucidate that

212 anges in the conformation of troponin in the thin filaments of skeletal muscle were followed during a

213 ilaments with uniform lengths, including the thin filaments of striated muscles and the spectrin-base

214 atory positions for tropomyosin cables along thin filaments on actin dominated by stereo-specific hea

215 , as a primary and versatile mediator of IFM thin-filament organization.

216 discharges since they do not form stratified thin-filament patterns.

217 Lmod2 null background rescued the elongated thin filament phenotype of HSPB7 KOs, but double KO mice

218 perative recruitment of cross bridges to the thin filament: phosphorylation of cardiac myosin binding

219 and its N-terminus extending out toward the thin filament pointed end.

220 ropomyosin fails to displace tropomodulin at thin filament pointed ends and fails to elongate thin fi

221 omodulin (Tmod) isoforms Tmod1 and Tmod4 cap thin filament pointed ends and functionally interact wit

222 vere model of DMD, Tmod1 disappears from the thin filament pointed ends in both tibialis anterior (TA

223 e are associated with loss of Tmod1 from the thin filament pointed ends, resulting in approximately 1

224 mics in myocytes by acting as a leaky cap at thin filament pointed ends.

225 by promoting actin assembly and dynamics at thin filament pointed ends.

226 tant in cardiomyocytes decreases leiomodin's thin-filament pointed-end assembly but does not affect t

227 No changes in thin filament protein phosphorylation were evident.

228 ntly implicated in NM, as well as a putative thin filament protein, leiomodin 3 (LMOD3).

229 Loss of sarcomere thin filament proteins is a frequent cause of NM; theref

230 Phosphorylation of thin filament proteins, such as troponin I and T, dramat

231 Mutations in thin-filament proteins have been linked to hypertrophic

232 ility assay to measure Ca(2+) sensitivity of thin filaments reconstituted with recombinant Tpm3.12 De

233 Our previous understanding of thin filament regulation had been limited to known movem

234 reorganization of the actin cytoskeleton and thin filament regulation to the myogenic response and se

235 e delicately poised energy balance governing thin filament regulation.

236 ) domain protein involved in skeletal muscle thin filament regulation.

237 uggesting the underlying structural basis of thin filament regulation.

238 herein we propose a novel model of skeletal thin filament regulation.

239 influences Tpm's location and, potentially, thin filament regulation.

240 tion causes DCM by altering Ca(2+)-dependent thin-filament regulation and that one of the possible HC

241 d in tropomyosin that ultimately perturb its thin filament regulatory function.

242 ltaGCIA, the energy barrier for activating a thin filament regulatory unit in the absence of Ca2+.

243 tions of protein-protein interactions in the thin-filament regulatory unit to sarcomere-level activat

244 We propose that regulatory proteins of the thin filament require the mechanical force of cycling my

245 of tropomyosin, likely disrupting the mutant thin filament response to calcium.

246 n by cRLC phosphorylation is mediated by the thin filament, revealing a signaling pathway between thi

247 e TNNI1 R37C mutation in human reconstituted thin filaments (RTFs) using fluorometry.

248 n vitro motility parameters of reconstituted thin filaments (RTFs).

249 s integrated analysis, spanning molecular to thin-filament scales, is capable of tracking the events

250 previously published all-atom models of the thin filament show chain separation and corruption of co

251 laments and displayed modes of motion on the thin filament similar to that of the Cy3-C0C3 fragment,

252 e the thin filament at low Ca(2+) but slowed thin filament sliding as much as the larger fragments.

253 metry and localization are preserved, native thin filament sliding over these thick filaments showed

254 n tropomyosin position and caused slowing of thin filament sliding.

255 ases in sarcomere length can reduce thick-to-thin filament spacing in skinned muscle fibers, thereby

256 in's effects on actin, apparently increasing thin-filament stiffness and ultimately depressing contra

257 t lower calcium levels is due to a change in thin filament structure.

258 ng a significant gap in our understanding of thin-filament structure and regulation.

259 t surface must be precisely tuned to overall thin-filament structure, function, and performance.

260 nked troponin-tropomyosin complexes over the thin filament surface, which uncovers or blocks myosin b

261 ion of troponin-tropomyosin strands over the thin filament surface.

262 ally occludes myosin binding sites along the thin filament surface.

263 Mutations in the cardiac thin filament (TF) have highly variable effects on the r

264 gor myosin is required to fully activate the thin filament (TF).

265 C2) can bind to and activate or inhibit the thin filament (TF).

266 C1mC2 induced larger structural changes in thin filaments than calcium activation, and these were s

267 backbone allowed it to attach more firmly to thin filaments than the wild-type isoform, providing evi

268 in filaments, and a structural change in the thin filaments that allows myosin motors from the thick

269 nge in the structure of the actin-containing thin filaments that allows the head or motor domains of

270 ealing a signaling pathway between thick and thin filaments that is still present when active force i

271 iding motility suggests that they form long, thin filaments that move rapidly away from a colony, ana

272 In the myosin-saturated state of the thin filament, there is a large additional shift in trop

273 ring thick-filament (MYH7mut, MYBPC3mut) and thin-filament (TNNT2mut, TNNI3mut) mutations, and IDCM w

274 of Tm along the actin (Ac):Tm:troponin (Tn) thin filament to block or expose myosin binding sites on

275 nt and a tight-binding mode to sensitize the thin filament to calcium, thus enhancing myosin binding.

276 We found that the K15N mutation desensitizes thin filaments to Ca(2+) and slows the kinetics of struc

277 tin and/or the myosin S2 domain, sensitizing thin filaments to calcium and governing maximal sliding

278 the thick filaments and on troponin C in the thin filaments to monitor structural changes in the myof

279 ts in the heart; it is essential for cardiac thin filaments to reach a mature length and is required

280 ults from calcium-activated sliding of actin thin filaments toward the centers of myosin thick filame

281 uctural working stroke in the head pulls the thin filament towards the centre of the sarcomere, produ

282 yosin cross-bridge binding to F-actin by the thin filament troponin (Tn)-tropomyosin (Tm) complex.

283 myosin cross-bridge cycling on actin by the thin filament troponin-tropomyosin complex.

284 ectron microscopy helical reconstructions of thin filaments, troponin density is mostly lost.

285 Tropomyosin (Tm) is an actin-binding, thin filament, two-stranded alpha-helical coiled-coil cr

286 treatment increased crossbridge proximity to thin filaments under all conditions.

287 simulations and experiments, and show that a thinning filament unexpectedly passes through a number o

288 e risk for incident development of HCM-LVSD (thin filament variants).

289 Regulated thin filament velocity measurements showed that the pres

290 a(2+) sensitizes the thin filament and slows thin filament velocity.

291 Direct visualization of mutant thin filaments via electron microscopy and 3-dimensional

292 thin filament, myosin S1-ADP binding to the thin filament was significantly affected by the same mut

293 generation that was associated with shorter thin filaments was compensated for by increasing the num

294 P-C enhances myosin recruitment to the actin-thin filament, we directly visualized fluorescently labe

295 sin complex only forms at the pointed end of thin filaments, where the tropomyosin N-terminus is not

296 nt structural change in the actin-containing thin filaments, which permits the binding of myosin moto

297 ansitions between runs and pauses of gliding thin filaments will occur at constant rate as given by a

298 f muscle differentiation; localized to actin thin filaments, with enrichment near the pointed ends; a

299 rge skeletal muscle protein wound around the thin filaments, with its C-terminus embedded within the

300 proportion to the overlap between thick and thin filaments, with no change in its interference fine