ライフサイエンスコーパス: fibril

1 type mice or purified GPI-anchorless amyloid fibrils).

2 teractions that would lead to mature amyloid fibrils.

3 an does not interact normally with cellulose fibrils.

4 n-prone sequence polymerizes to form regular fibrils.

5 elongated cell shape and migration along the fibrils.

6 olecular weight oligomers, protofibrils, and fibrils.

7 rotoxic oligomers and assembles into amyloid fibrils.

8 utes to the stretching of fibronectin matrix fibrils.

9 alphaS fibrils relative to wild-type alphaS fibrils.

10 sults from the addition of ThT-positive SOD1 fibrils.

11 he protein toward the formation of insoluble fibrils.

12 and amyloid beta proteins into oligomers and fibrils.

13 me for initiating self-assembly into amyloid fibrils.

14 basement membrane zone forming the anchoring fibrils.

15 sor p53 rapidly aggregate but form amorphous fibrils.

16 ost likely by binding to the ends of growing fibrils.

17 susceptibility to exogenous alpha-synuclein fibrils.

18 ich produces a high yield of genuine amyloid fibrils.

19 gregation without the need for exogenous Tau fibrils.

20 l-helical fold organized into highly ordered fibrils.

21 ta11-x fibrils than full-length amyloid-beta fibrils.

22 llel beta-sheet structure observed in mature fibrils.

23 ely 218 nm band usually observed for amyloid fibrils.

24 ne the structural heterogeneity found in the fibrils.

25 tions affect the organization of alphaS into fibrils.

26 te the water interactions of several Abeta40 fibrils.

27 vier beads produced faster rates and shorter fibrils.

28 omers showed their colocalization in racemic fibrils.

29 oform polymerizes into highly stable amyloid fibrils.

30 es whereas linear Abeta(14-23) monomers form fibrils.

31 for protein folding and assembly of amyloid fibrils.

32 cleation dependent mechanism to form amyloid fibrils.

33 fective at inhibiting seeding by full-length fibrils.

34 ding mechanism of small molecules to amyloid fibrils.

35 to monomers prior to rearranging to amyloid fibrils.

36 ely different, highly misfolded amyloid-like fibrils.

37 eripheral injection of various mutant alphaS fibrils.

38 peptide region compared with intact collagen fibrils.

39 dulated to favor nontoxic fibrils over toxic fibrils.

40 ith the formation of alpha-synuclein amyloid fibrils.

41 thus accelerates the formation of non-toxic fibrils.

42 0P, E46K, G51D, and A53T) on alpha-synuclein fibrils.

43 izing structural features of alpha-synuclein fibrils.

44 transition of the small Abeta40 oligomers to fibrils.

45 osomes/lysosomes ruptured by endocytosed tau fibrils.

46 likely reflects an intrinsic property of Tau fibrils.

47 d undergoes recycling and incorporation into fibrils, a process dependent on TbetaRII.

48 We discover that fibrils accumulate towards the hot side of the channel a

49 A pathogenic role for alpha-syn fibril accumulation is supported by the identification o

50 I collagen, the major component of anchoring fibrils (AF).

51 tion of scFvs with high affinity for Abeta42 fibrils after removal of scFvs that bind Abeta42 in its

52 Intraperitoneal injection of alphaS fibrils also induced CNS alphaS pathology in another alp

53 he recognition of monomeric, oligomeric, and fibril amyloid-beta (Abeta) by three homologous antibodi

54 In addition to protein fibrils, amyloid plaques also contain non-proteinaceous

55 t focuses on conformational requirements for fibril and nucleus elongation.

56 salt-bridge, a major feature of the Abeta40 fibrils and a focal point of mutations linked to early o

57 is first-order in the concentration of Abeta fibrils and a pseudo-first-order reaction in the concent

58 d promoted the self-assembly of ThT-negative fibrils and amorphous complexes.

59 Ls were used to examine the effects of Abeta fibrils and brain-derived tau oligomers on AD-related ge

60 l features with structures reported for IAPP fibrils and demonstrate the importance of hydrogen bondi

61 eraction between the alpha-synuclein amyloid fibrils and heparan sulfate and show that overall sulfat

62 s diminished self-assembly into ThT-positive fibrils and instead promoted the self-assembly of ThT-ne

63 e modulates their self-assembly into amyloid fibrils and may link the pathogeneses of these two cell-

64 Fibrils and oligomers are the aggregated protein agents

65 the islet amyloid polypeptide (IAPP) to form fibrils and oligomers is important in the progression of

66 uscular (i.m.) routes of injection of alphaS fibrils and other protein controls.

67 ies have shown that Apo-CII can form amyloid fibrils and that certain mutations in this protein promo

68 ay a key role in the cytotoxicity of amyloid fibrils and the pathogenesis of neurodegenerative diseas

69 tween the length distribution of the amyloid fibrils and their ability to induce the heritable [PSI(+

70 n our knowledge of the structures of amyloid fibrils and their oligomeric precursors and of the mecha

71 membranes are packed with electron-dense RNA fibrils and their volumes are closely correlated with RN

72 of xylan with hydrophilic faces of cellulose fibrils, and is essential for development of normal plan

73 of Zn(+2), both of these fail to form proper fibrils, and the salt bridge remains disrupted.

74 ing candidate scFvs that bind to the Abeta42 fibrils; and (iii) kinetic screening and analysis to fin

75 uMAPPS retrieves pixel-by-pixel the collagen fibrils anisotropy and orientation by operating directly

76 tivity, we explain how dimensions of amyloid fibrils are able to modulate their infectious potential

77 Because propagation-active fibrils are chemically indistinguishable from innocuous

78 o in a seeding-like manner and the resulting fibrils are composed of both peptides.

79 Here we observe that hIAPP fibrils are cytotoxic to cultured pancreatic beta-cells,

80 sis, have become particularly relevant since fibrils are formed in vitro in physiologically relevant

81 In contrast, E46K alphaS fibrils are intrinsically inefficient at seeding alphaS

82 erved within the aggregation end products of fibrils are known to arise due to microstructural differ

83 The collagen fibrils are oriented radially with an apically directed

84 FN fibrils are the primary component in primordial ECM and,

85 These threads (fibrils) are capable of growing on the ends by seeding t

86 t off-pathway oligomers, rather than amyloid fibrils, are the toxic species regardless of the pathoge

87 erized by the presence of cross-beta amyloid fibrils as well as the loss of neuronal or pancreatic be

88 Learning how PMEL fibrils assemble without apparent toxicity may help deve

89 tructure and dimensions of synthetic amyloid fibrils assembled from the yeast (Saccharomyces cerevisi

90 igomerization, secondary structure dynamics, fibril assembly dynamics, and fibril morphology.

91 try and demonstrates a mechanism by which FN fibril assembly regulates traction force dynamics in res

92 These include fibrils associated with systemic and neurodegenerative d

93 c alpha helices stacked perpendicular to the fibril axis into tight self-associating sheets.

94 orm an infinite metal-ligand chain along the fibril axis.

95 nt assemblies, including liquid droplets and fibril-based hydrogels.

96 not known exactly where amyloid-beta (Abeta) fibrils begin to accumulate in individuals with Alzheime

97 Vangl2 and Ptk7 In wild-type mice, collagen-fibril bundles appear within a tectorin-based matrix at

98 ced in both Het-s/GroEL aggregates and Het-s fibrils, but virtually completely eliminated in Het-s/Gr

99 favoring the formation of a specific type of fibril by binding to aggregates formed early on one of m

100 characteristics of multiple mutant htt exon1 fibrils by complementary techniques, including infrared

101 c mineralization was observed along collagen fibrils by electron microscopy in both groups, Raman mic

102 While numerous proteins form fibrils by prion-like seeded polymerization in vitro, on

103 Amyloid fibrils can be much more stable than other protein assem

104 find the scFvs that inhibit selectively the fibril-catalyzed secondary nucleation process in Abeta42

105 es are helically displayed on the surface of fibrils, comparable to polymerized nucleic acids.

106 rders are characterized by deposition of tau fibrils composed of conformers (i.e. strains) unique to

107 oEL binds to the mobile regions of the Het-s fibril comprising the N-terminal tail and a loop connect

108 A specific fibril conformation and the resulting formation of the c

109 py revealed molecular-level perturbations of fibril conformation by the PD-related mutations that are

110 We show evidence that 1-108-alphaS fibrils consist of strongly twisted beta-sheets with an

111 Short fibrils constitute the major species of seed-competent T

112 , has led to controversial assumptions about fibril constitution, and it is unclear to-date what the

113 LC), a segment of only 57 residues forms the fibril core, while other segments remain dynamically dis

114 ported that in-plane orientation of collagen fibrils could be determined by modulating the polarizati

115 ied four scFvs that inhibit specifically the fibril-dependent secondary nucleation process.

116 The polymorphic fibrils differ in their flanking domains rather than the

117 yo-TEM, used together with SAXS to determine fibril dimensions, shows that the length and degree of t

118 Rate equations on fibril disappearance are deduced from a simple model, wh

119 us with wild-type, H50Q, G51D or A53E alphaS fibrils displayed induction of alphaS inclusion patholog

120 tion of a fully H-bonded beta-hairpin at the fibril edge while interfering with H-bonding to the next

121 lation existed between bead mass and rate of fibril elongation (R(2) = 0.7): heavier beads produced f

122 f initial fibril formation, but the stage of fibril elongation is affected mainly by the length of C-

123 ion, but did not markedly affect the rate of fibril elongation.

124 : namely, the initial monomer binding to the fibril end (charge-dependent, relatively fast), and the

125 features common to both Abeta oligomers and fibril ends and that this interaction could contribute t

126 nt balance between ordered nanostructure and fibril entanglement.

127 ture of PNFs, the mechanisms associated with fibril-fibril interactions and their assembly into macro

128 on of Abeta42 (the 42-residue form of Abeta) fibrils, fibrillar alpha-synuclein catalyses the heterog

129 ring the transition from the oligomer to the fibril form.

130 sh a new modality for covalent inhibition of fibril formation and illuminate a path for future optimi

131 ata demonstrate that Aha1 contributes to tau fibril formation and neurotoxicity through Hsp90.

132 The early stages of fibril formation are difficult to capture in solution.

133 This diboronic acid inhibits fibril formation by both wild-type TTR and a common dise

134 Although acidic pH promotes amyloid fibril formation by this and many other proteins, the mo

135 However, fitting kinetic fibril formation data to a complex model including expli

136 h affinities of 1-10 nm and inhibit AbetapE3 fibril formation in vitro.

137 Fibril formation involves a spontaneous nucleation event

138 In this work, we compare fibril formation of alphaS and betaS at pH 7.3 and mildl

139 e importance of these charged side chains in fibril formation of betaS.

140 s a transient intermediate to beta-sheet and fibril formation of pEAbeta (3-42).

141 Owing to the enhanced fibril formation propensity, racemic Abeta42 was less pr

142 show dramatically altered pH sensitivity for fibril formation supporting the importance of these char

143 mine how this pattern is generated, collagen-fibril formation was examined in mice lacking a tectorin

144 hown with AFM imaging that the inhibition of fibril formation was not complete with any of the compou

145 e insights into polyQ solution structure and fibril formation while also suggesting an approach to th

146 During amyloid fibril formation, amyloidogenic polypeptides misfold and

147 ordered protein aggregation, such as amyloid fibril formation, and not with stable molten globules st

148 se folding intermediates, which occur during fibril formation, are the toxic species in the amyloid-r

149 ay an important role at the stage of initial fibril formation, but the stage of fibril elongation is

150 insights into how polyphenols inhibit Abeta fibril formation, knowledge that could be useful for des

151 tide motif in repeat R3, a crucial motif for fibril formation, shows strikingly low variability of al

152 heir equimolar mixing to lead to accelerated fibril formation.

153 ified in vivo, whereas its absence abrogates fibril formation.

154 Abeta, while dimers strongly suppress Abeta fibril formation.

155 mechanistic effects of modulators on amyloid fibril formation.

156 predict the resulting traction force and FN fibril formation.

157 leation enabling dimerisation and subsequent fibril formation.

158 s prior to the "downhill" folding leading to fibril formation.

159 ge molar excess, completely prevents amyloid fibril formation.

160 earliest stages of aggregation, well before fibril formation.

161 role of Abeta's N-terminal domain in amyloid fibril formation.

162 into a well-defined structural element upon fibril formation.

163 of prefibrillar species formed early during fibril formation.

164 than doxycycline with complete abrogation of fibril formation.

165 tive structures, Abeta42 fibrils, or amyloid fibrils formed from other sequences.

166 in the formation and accumulation of amyloid fibrils formed from pathogenic variants of human lysozym

167 nder) to detect soluble oligomers and mature fibrils formed from recombinant alpha-syn protein contai

168 , we have characterized the structure of the fibrils formed from truncated tau for the first time.

169 eoliposomes, and strikingly, several thinner fibrils formed ordered bundles that either covered the s

170 ructural core and external morphology of the fibrils formed.

171 Our data reveal that oligomers of the fibril-forming peptide segments VEALYL and YVEALL, which

172 n-electron resonance measurements of two key fibril-forming regions of tau, PHF6 and PHF6*, in transi

173 l cation and a phenyl ring stabilized by the fibril framework.

174 tients with t-AD and PCA-AD, whereas Abeta40 fibrils from r-AD samples exhibit a significantly greate

175 been proposed as the mechanism by which CysC fibrils grow.

176 ucidate structural requirements of alpha-syn fibril growth and to identify growth inhibitors as a pot

177 onomers associate to form seeds, followed by fibril growth during which monomeric alpha-syn molecules

178 onomer association (SeGMA) assays to measure fibril growth over 3 h in the presence of C2-alpha-syn m

179 The 1-108-alphaS fibrils have a unique negative circular dichroism band a

180 s that lead to the formation of amyloid beta fibrils implicated in Alzheimer's disease, gamma-secreta

181 morphology with higher affinity than Abeta40 fibrils in alternative structures, Abeta42 fibrils, or a

182 lucidating the role of these beta-sheet-rich fibrils in disease progression is crucial; however, coll

183 The collagen fibrils in Fam20C-deficient bone were disorganized and t

184 Intraperitoneal (i.p.) injections of alphaS fibrils in hemizygous M83 transgenic (M83(+/-)) mice res

185 tive diseases and cancer, functional amyloid fibrils in microorganisms and animals, and many denature

186 t internalization of alpha-synuclein amyloid fibrils in neuroblastoma cells is dependent on heparan s

187 accumulation of alpha-synuclein (alpha-syn) fibrils in neuronal inclusions is the defining pathologi

188 nd further boosted by incorporating collagen fibrils in PDMS-HDA.

189 Our findings suggest that amyloid fibrils in semen may play a role in reproduction by part

190 art of the Phe521Leufs chain is deposited as fibrils in the patient's kidneys, establishing that only

191 We show that VLITL forms typical amyloid fibrils in vitro and is a major signal for cross-beta-sh

192 de spanning this sequence forms amyloid-like fibrils in vitro and is capable of inducing the conversi

193 eat resulted in a peptide that rapidly forms fibrils in vitro.

194 Data for Abeta42 fibrils indicate structural heterogeneity in most sample

195 Surprisingly, the fibrils inhibited fertilization by immobilizing sperm.

196 hy was fully developed already 10 days after fibril injection, accompanied by progressive degeneratio

197 Mutations of key crystal fibril interface residues in viruses encoding full-lengt

198 tes (mPPCs) that disassemble preformed Abeta fibrils into dispersible sub-100 nm structures.

199 ed by pH-induced assembly/disassembly of the fibrils into random coils.

200 licating properties of proteins into amyloid fibrils is a common phenomenon and underlies a variety o

201 he amyloid beta peptide (Abeta) into amyloid fibrils is a defining characteristic of Alzheimer's dise

202 synuclein into beta-sheet-rich oligomers and fibrils is associated with multiple neurodegenerative di

203 ein fibronectin (FN) into elastic, insoluble fibrils is still poorly understood.

204 ynuclein (alphaS) into oligomers and amyloid fibrils is well established, the aggregation propensity

205 rminal end of the first beta-strand of Het-s fibrils, is significantly reduced in both Het-s/GroEL ag

206 region loops can effectively bind the Abeta fibril lateral surface around the same 13-16 region.

207 reorganized by a stacking procedure to form fibril-like and granular nanostructures.

208 We find that curcumin allows fibril-like structures containing the salt bridge to eme

209 crowns were associated with long cytoplasmic fibrils, likely to be exported progeny RNA.

210 nucleation and elongation into amyloid-like fibrils linked to amyotrophic lateral sclerosis.

211 We also report this arrangement of fibrils made by proteoliposomes bearing CesA8 from hybri

212 gomer solutions into mice to form a collagen-fibril matrix at body temperature.

213 pulated oligomers formed en route to amyloid fibrils may constitute the most toxic aggregates associa

214 assays of SOD1 that enable the control over fibril morphologies and produce eightfold faster lag tim

215 of multiple human Tauopathies with distinct fibril morphologies has led to the suggestion that diffe

216 ture dynamics, fibril assembly dynamics, and fibril morphology.

217 The model accurately predicts FN fibril morphometry and demonstrates a mechanism by which

218 ) specifically inhibited elongation of Abeta fibrils, most likely by binding to the ends of growing f

219 of alpha-synuclein monomers into the amyloid fibril: namely, the initial monomer binding to the fibri

220 g is capped by GroES interact with the Het-s fibrils; no evidence is seen for any interaction with fo

221 ligomers neither readily convert into mature fibrils nor bind lipid surfaces via their amphipathic al

222 ffect of each acyl group on the rate of SOD1 fibril nucleation and elongation were quantified in vitr

223 hin a tectorin-based matrix at E15.5 and, as fibril number rapidly increases, become co-aligned and c

224 e, functional protein into insoluble amyloid fibril occurs via a complex process involving the initia

225 wo morphologically different alpha-synuclein fibrils, one helical and the other ribbon-like, are show

226 Aggregation of amyloid-beta peptides into fibrils or other self-assembled states is central to the

227 0 fibrils in alternative structures, Abeta42 fibrils, or amyloid fibrils formed from other sequences.

228 n the ECM is organized into large bundles of fibrils, or collagen cables, and the number of these cab

229 le X-ray scattering allows us to monitor the fibril orientation in the microchannel and compare the a

230 if any, role in determining normal collagen-fibril orientation; however, evidence from tectorin-knoc

231 red peptide to mature amyloid twisted-ribbon fibrils over a few hours when incubated on polystyrene p

232 eaction could be modulated to favor nontoxic fibrils over toxic fibrils.

233 rent binding modes to the surface of amyloid fibrils paves the way for better understanding of the bi

234 ed fluorescently labeled alpha-syn preformed fibrils (pffs) in conjunction with the membrane-impermea

235 erebral injections of either T40PL preformed fibrils (PFFs) or AD-tau seeds into T40PL-GFP mice induc

236 d widths, linking aggregation propensity and fibril polymorphism.

237 ult of faster aggregation, but also of which fibril polymorphs are preferentially formed when the C-t

238 lar environment, our data would suggest that fibril polymorphs can be formed in different cellular co

239 ng the mechanism of the formation of various fibril polymorphs with differing cytotoxic effects is es

240 binding site models predict a heterogeneous fibril population that contains two distinct phenotypes

241 LFAO-seeded fibrils possess distinct morphology made of repeating LF

242 The data explain why rigid collagen fibrils potentiate PI3K activation to promote malignancy

243 (ssNMR) measurements on Abeta40 and Abeta42 fibrils prepared by seeded growth from extracts of Alzhe

244 on to oocyte led us to examine whether these fibrils promote fertilization.

245 Here we report fibril propagation of an Abeta42 dodecamer called large

246 e the non-micellar phase promotes on-pathway fibrils, pseudo-micellar and micellar phases promote pre

247 arly injected with H50Q, G51D or A53E alphaS fibrils relative to wild-type alphaS fibrils.

248 indicate, therefore, that LMWH binding to 3Q fibrils requires a precise molecular complementarity of

249 distinct beta-sheet structure, 1-108-alphaS fibrils resist incorporation of WT-alphaS monomers.

250 omolog beta-synuclein (betaS) is essentially fibril-resistant under cytoplasmic physiological conditi

251 ed to the formation of oligomers and amyloid fibrils, respectively.

252 ment of cell-dependent forces to generate FN fibrils restricts investigation of the mechanism of asse

253 experiment is demonstrated on an M0Abeta1-42 fibril sample that yields high-quality data that is read

254 Conversely, E46K alphaS fibril seeding was significantly delayed and less effici

255 inson's disease by injecting human alpha-syn fibril seeds into the rat substantia nigra (SN), in comb

256 the length and degree of twisting of peptide fibrils seem to be influenced by the net peptide charge.

257 Our results suggest that Abeta fibrils start to accumulate predominantly within certain

258 ggregation times appear to facilitate unique fibril structure as determined by the highly reproducibl

259 existence of a specific predominant Abeta40 fibril structure in t-AD and PCA-AD, suggest that r-AD m

260 ents suggest that variations in amyloid-beta fibril structure in vivo may correlate with variations i

261 8 individuals, we find that a single Abeta40 fibril structure is most abundant in samples from patien

262 strands, and then partially disorders in the fibril structure.

263 two engineered beta-solenoid protein mutant fibril structures (spruce budworm and Rhagium inquisitor

264 , suggest that r-AD may relate to additional fibril structures and indicate that there is a qualitati

265 Computational models of betaS fibril structures indicate that key glutamate residues (

266 ns to compare previously proposed calcitonin fibril structures.

267 rtually completely eliminated in Het-s/GroEL fibrils, suggesting that in the latter, GroEL may come i

268 tes the degree of plaque compaction, amyloid fibril surface area, and insulation from adjacent axons

269 he GAG and charged residues displayed on the fibril surface.

270 showed that xyloglucans were associated with fibril surfaces in both extended and coiled conformation

271 probe long-range heteronuclear contacts for fibrils templated from a 1:1 mixture of (13)C- and (15)N

272 ully lysine-alkylated aS (acetyl-aS); and aS fibrils, testing their ability to be chemically modified

273 ongly with pyroglutamylated amyloid-beta11-x fibrils than full-length amyloid-beta fibrils.

274 vity in the interactions of the GAG with the fibril that extends beyond general electrostatic complem

275 an atomic-level structural model for FUS LCD fibrils that answers some questions and raises new ones.

276 er negligible fibrillogenesis or produces FN fibrils that are neither robust nor physiological.

277 olypeptide (hIAPP) aggregate to form amyloid fibrils that deposit in tissues and are associated with

278 tion into monomers leads to the formation of fibrils that underlie human amyloidogenic diseases.

279 ecognize (monomers, oligomers, protofibrils, fibrils), the consequences of targeting different specie

280 However, in the case of amyloid fibrils, the biphasic region is too small to be experime

281 stly likely that the mPPCs disassemble Abeta fibrils through a direct interaction.

282 FN) is an important ECM component that forms fibrils through cell contacts and creates directionally

283 Herein, we constructed helical fibrils through chiral self-assembly of nucleobase-pepti

284 without interfering with its ability to form fibrils, thus providing powerful tools for uncoupling th

285 The addition of ThT-negative, acylated SOD1 fibrils to organotypic spinal cord failed to produce the

286 bit the ability of exogenous full-length tau fibrils to seed intracellular tau in HEK293 biosensor ce

287 Following alpha-synuclein fibril treatment, neurons deficient in TMEM175 were foun

288 e (wt) CysC will also aggregate into amyloid fibrils under some conditions.

289 d protein Tau to a highly structured amyloid fibril underlies human Tauopathies.

290 GroEL binds to the Het-s fibrils via its apical domain located at the top of the

291 lly accelerated aggregation leading to large fibrils visualized by electron microscopy of pEAbeta (3-

292 In comparison, i.m. injection of alphaS fibrils was more efficient in inducing CNS alphaS pathol

293 nfer transmissibility to prion protein (PrP) fibrils, we have analyzed synthetic PrP amyloids with or

294 r TTR and inhibition of its tendency to form fibrils were coupled with X-ray crystallographic analysi

295 in precipitated out as a network of hydrated fibrils which could be hand-kneaded into a viscoelastic

296 and a higher solvent exposure than WT-alphaS fibrils, which is also indicated by the pronounced diffe

297 cular-weight heparin (LMWH) binds to Abeta40 fibrils with a three-fold-symmetric (3Q) morphology with

298 ion experiments generate limiting scissioned fibrils with a well-defined length-to-width correlation

299 Nonetheless, fibrils with parallel molecules show bulky loops formed

300 The beta-sheet self-assembles to form long fibrils with the hydrophobic edge and histidine residues