ライフサイエンスコーパス: eIF2B

1 eIF2B acts as a guanine nucleotide exchange factor (GEF)

2 eIF2B controls the recruitment of the initiator methiony

3 eIF2B facilitates and controls protein synthesis in euka

4 eIF2B is a five-subunit guanine nucleotide exchange fact

5 eIF2B is a heteropentameric guanine-nucleotide exchange

6 eIF2B is an essential multi-subunit factor and a major t

7 eIF2B is comprised of catalytic and regulatory subcomple

8 eIF2B is the heteropentameric guanine nucleotide exchang

9 eIF2B is unusually complex with five subunits (alpha-eps

10 eIF2B mutations predominantly affect the brain white mat

11 eIF2B(alphabetagammadeltaepsilon)2 decamers show greater

12 eIF2B, the nucleotide exchange factor for eIF2, is a het

13 eIF2B-related disorders have a clinical spectrum ranging

14 eukaryotic translation initiation factor 2B (eIF2B) and the very-long-chain fatty acid (VLCFA) synthe

15 bunits of eukaryocytic initiation factor 2B (eIF2B) are the cause of vanishing white-matter disease/c

16 Eukaryotic translation initiation factor 2B (eIF2B) is a five-subunit complex that catalyzes guanine

17 Eukaryotic translation initiation factor 2B (eIF2B) is a heteropentameric guanine nucleotide exchange

18 Eukaryotic translation initiation factor 2B (eIF2B) is the guanine nucleotide exchange factor (GEF) f

19 Eukaryotic initiation factor 2B (eIF2B) is the guanine nucleotide exchange factor for eIF

20 Eukaryotic translation initiation factor 2B (eIF2B) is the heteropentameric guanine nucleotide exchan

21 Eukaryotic initiation factor 2B (eIF2B) plays a key role in protein synthesis and in its

22 eukaryotic translation initiation factor 2B (eIF2B) provides a fundamental controlled point in the pa

23 Eukaryotic initiation factor 2B (eIF2B), a five-subunit guanine nucleotide exchange facto

24 control of eukaryotic initiation factor 2B (eIF2B), a multisubunit guanine nucleotide exchange facto

25 K-3beta is translation initiation factor 2B (eIF2B), linking global regulation of protein synthesis t

26 tations in translation initiation factor 2B (eIF2B).

27 eukaryotic translation initiation factor 2B (eIF2B).

28 eukaryotic translation initiation factor 2B (eIF2B).

29 ced hypertrophy does not depend on GSK-3beta/eIF2B signaling.

30 ow ISRIB-mediated stabilization of activated eIF2B dimers, and suggest that eIF2B4 (delta-subunit) co

31 or amino acids, insulin no longer activates eIF2B.

32 by facilitating the assembly of more active eIF2B.

33 s, suggesting that these substitutions allow eIF2B to accept phosphorylated eIF2 as a substrate for n

34 2, around the phosphorylation site, allowing eIF2B to detect and respond to phosphoserine at residue

35 contrast, the GCD1 and GCD6 subunits form an eIF2B subcomplex that binds equally to eIF2 and eIF2(alp

36 Two eIF2 molecules bind opposite sides of an eIF2B hetero-decamer through eIF2alpha-D1, which contain

37 Our reporter-based shRNA screen revealed an eIF2B requirement for ISRIB activity.

38 g an affinity-binding assay, we show that an eIF2B subcomplex of the GCN3, GCD7, and GCD2 subunits bi

39 ons of eIF2B(alphabetagammadeltaepsilon) and eIF2B(betagammadeltaepsilon) complexes, with important i

40 Cross-links between eIF2 and eIF2B allow modelling of interactions that contribute to

41 SRIB targets an interaction between eIF2 and eIF2B that lies at the core of the ISR.

42 for structural interactions between eIF2 and eIF2B that promote wild-type rates of nucleotide exchang

43 n(s) of eIF2 in the absence of eIF2alpha and eIF2B and are consistent with the idea that the latter f

44 he delta- and epsilon-subunits of eIF2B, and eIF2B was shown to bind only to the beta-subunit of eIF2

45 Dual and reciprocal modulation of eIF4F and eIF2B was leucine-specific because isoleucine, a structu

46 mediate the binding of eIF2 to both eIF5 and eIF2B.

47 egulated by eIF5 (GAP and GDI functions) and eIF2B (GEF and GDF activities), while eIF2alpha phosphor

48 dissociation inhibitor (GDI) functions, and eIF2B is the guanine nucleotide exchange factor (GEF).

49 tors of eIF2 function, eIF2alpha kinases and eIF2B, have evolved to recognize the same surface and ov

50 alterations in global protein synthesis and eIF2B activity were maintained in the presence of the ho

51 eraction is specifically between YBR159W and eIF2B and not between other members of the translation i

52 oplasmic reservoir for eIF2 that antagonizes eIF2B-promoted guanine nucleotide exchange, enabling coo

53 alpha subunit of eIF2 directly contacts any eIF2B subunits or whether this interaction is modulated

54 e to endoplasmic reticulum stress attenuates eIF2B activity by phosphorylating eIF2alpha, suggesting

55 These data uncover competition between eIF2B and eIF5 for TC and identify that phosphorylated e

56 itical for interprotein interactions between eIF2B subunits necessary for eIF2B complex formation.

57 pose a model for domain interactions between eIF2B subunits.

58 opy (cryo-EM) showed that engagement of both eIF2B regulatory sites by two eIF2(alphaP) molecules rem

59 ine triphosphatase that becomes activated by eIF2B, a two-fold symmetric and heterodecameric complex

60 er (VWM) is a neurological disease caused by eIF2B mutations that, like phosphorylated eIF2, reduce i

61 serine-51, inhibiting nucleotide exchange by eIF2B.

62 n intermediate complexes can be inhibited by eIF2B.

63 /Gcd7 is crucial for binding of substrate by eIF2B in vivo, beyond its dispensable regulatory role in

64 terestingly, the same conditions that bypass eIF2B also overcome the requirement for the normally ess

65 Consistent with bypassing eIF2B, these conditions also suppress the lethal effect

66 e identification of regulatory and catalytic eIF2B subcomplexes leads us to propose that binding of e

67 th null mutations in the VLCFA pathway cause eIF2B to appear as numerous foci throughout the cytoplas

68 ated eIF2 [eIF2(alphaP)] and to characterize eIF2B regulatory mutations that render translation initi

69 unphosphorylated eIF2, eIF5 can out-compete eIF2B to stabilize TC/eIF5 complexes.

70 the eukaryotic initiation factor 2B complex (eIF2B).

71 on refolds eIF2alpha, allowing it to contact eIF2B at a different interface and, we surmise, thereby

72 In contrast, eIF2B activity remained unchanged in response to AICAR t

73 In contrast, eIF2B lacking the alpha-subunit is insensitive to inhibi

74 unknown, regulatory mechanisms that control eIF2B activity.

75 ssays show that this 'switch-helix' controls eIF2B activity and signaling.

76 of eIF2B subunits, we identified cytoplasmic eIF2B bodies in mammalian cells.

77 is attenuated by mutations that desensitize eIF2B to the inhibitory effect of eIF2(alphaP).

78 TC/eIF5 is formed with phosphorylated eIF2, eIF2B outcompetes eIF5 and destabilizes TC.

79 ukaryotic translation initiation factor eIF2-eIF2B complex, reversed the changes in translation and i

80 action with eIF2B to such effect that p-eIF2-eIF2B association can be selectively inhibited.

81 acting as a competitive inhibitor of p-eIF2-eIF2B interaction.

82 hange and initiator tRNA binding to the eIF2/eIF2B complex.

83 Unlike wild-type eIF2B, eIF2B complexes with mutated GCN3 or GCD7 subunits effic

84 ment with this, archaea appear to lack eIF5, eIF2B and the lysine-rich binding domain for these facto

85 No differences were noted with either eIF2B or eIF2 alpha.

86 protein synthesis initiation in eukaryotes, eIF2B is the guanine-nucleotide exchange factor for eIF2

87 ms bound with its nucleotide exchange factor eIF2B by electron cryomicroscopy.

88 5 and the guanine-nucleotide exchange factor eIF2B modulate eIF2 function through direct interactions

89 rs the eIF2-specific guanine exchange factor eIF2B to block eIF2 recycling, thereby halting translati

90 ion of eIF2 with its GTP-GDP exchange factor eIF2B.

91 ty of the guanine nucleotide-exchange factor eIF2B.

92 e GTP form by the nucleotide exchange factor eIF2B.

93 leading to inhibition of its exchange factor eIF2B.

94 CREB) protein, translation-initiation factor eIF2B, and the nucleolar p53-interacting protein nucleos

95 ge activity of translation initiation factor eIF2B.

96 the activity of eukaryotic initiation factor eIF2B.

97 inhibition of translation initiation factor eIF2B.

98 whereas eIF2.GDP binds the pentameric factor eIF2B for guanine nucleotide exchange.

99 on AUG codon recognition, whereas the factor eIF2B promotes guanine nucleotide exchange on eIF2 to re

100 ely the sugar isomerases, translation factor eIF2B, ligand-binding domains of the DeoR-family transcr

101 ion with guanine nucleotide exchange factor (eIF2B) are described.

102 r of its guanine nucleotide exchange factor, eIF2B, impairing formation of the ternary complex and th

103 with the guanine nucleotide exchange factor, eIF2B, is a key mechanism for controlling translation un

104 bits its guanine nucleotide exchange factor, eIF2B.

105 r of its guanine nucleotide exchange factor, eIF2B.

106 P by the complex nucleotide exchange factor, eIF2B.

107 the activity of eIF2 are translation factors eIF2B and eIF5, thought to primarily function with eIF2-

108 ast to other translation initiation factors, eIF2B and eIF2 colocalize to a specific cytoplasmic locu

109 First, eIF2B GDF is insensitive to eIF2alpha phosphorylation, u

110 on with its substrate, eIF2, in vivo and for eIF2B activity in vitro.

111 g that the higher affinity of eIF2alphaP for eIF2B drives translational control.

112 Mutations in the genes for eIF2B cause an often severe neurological disorder, "vani

113 actions between eIF2B subunits necessary for eIF2B complex formation.

114 initiator tRNA, overcome the requirement for eIF2B in vivo.

115 eract with the eIF2 complex, a requisite for eIF2B inhibition by eIF2alpha phosphorylation.

116 toxicity, presumably by titrating GCN3 from eIF2B and producing the four-subunit form of eIF2B that

117 cluding GCN3, the nonessential subunit, from eIF2B; thus, all three proteins are critical for regulat

118 the guanine-nucleotide exchange factor (GEF) eIF2B.

119 of guanine nucleotide exchange factor (GEF) eIF2B.

120 with the eIF2 guanine exchange factor (GEF), eIF2B.

121 ts guanine nucleotide exchange factor (GEF), eIF2B.

122 terized 29 novel mutations in the homologous eIF2B subunits encoded by GCD2, GCD7, and GCN3 that redu

123 dditionally, beta/Gcd7 mutations that impair eIF2B function display extensive allele-specific interac

124 Notably, impaired eIF2B activity induced by PERK activation in oligodendro

125 point to a cell-autonomous role of impaired eIF2B activity in myelinating oligodendrocytes in the pa

126 rylating eIF2alpha, suggesting that impaired eIF2B activity in oligodendrocytes induced by VWMD mutat

127 eIF5 and TC/eIF5 complexes, thereby impeding eIF2B reaction and MFC formation, respectively.

128 The changes in eIF2B activity could be explained in part by modulation

129 possibly due to the occurrence of defects in eIF2B that overcome the inhibitory effects of eIF2alpha

130 that these segments form a single domain in eIF2B that makes multiple contacts with the alpha subuni

131 lf of GCD2 comprise the regulatory domain in eIF2B.

132 GCD7, and GCN3 perform related functions in eIF2B regulation.

133 In addition, inherited mutations in eIF2B cause a fatal leukoencephalopathy.

134 of eIF2alpha and a concomitant reduction in eIF2B activity in perfused livers from wild-type mice, b

135 Gcn2p phosphorylates eIF2 to inhibit eIF2B.

136 P-eIF2alpha inhibits eIF2B, the guanine nucleotide exchange factor that recyc

137 In eukaryotic translation initiation, eIF2B is the guanine nucleotide exchange factor (GEF) re

138 It was shown previously that the largest eIF2B subunit, eIF2Bepsilon, is the only single subunit

139 F2B function by mutation and in fact lowered eIF2B activity in strains lacking eIF2(alphaP).

140 at the composition and function of mammalian eIF2B bodies are regulated by the ISR and the drugs that

141 t, catalytic, subunit (epsilon) of mammalian eIF2B.

142 ed the subunit interactions within mammalian eIF2B by using a combination of mass spectrometry and in

143 By modulating eIF2B function, ISRIB promises to be an invaluable tool

144 y, long-term treatment with a small molecule eIF2B activator, 2BAct, prevents all measures of patholo

145 stimulates the remaining activity of mutant eIF2B complex in vivo, abrogating the maladaptive stress

146 d prevents the latter from inhibiting native eIF2B.

147 e toxicity of eIF2(alphaP) and rescue native eIF2B function when overexpressed with delta/Gcd2 or gam

148 educing epsilon/Gcd6 abundance in the native eIF2B-eIF2 holocomplex.

149 Expression of nonphosphorylatable eIF2B prevented cytochrome c release resulting from PI 3

150 survival, expression of nonphosphorylatable eIF2B prevented inhibition of protein synthesis followin

151 with VWM carrying mutations in subunit 5 of eIF2B (encoded by EIF2B5).

152 ve found that ISRIB-mediated acceleration of eIF2B's nucleotide exchange activity in vitro is observe

153 the effects of pharmacological activation of eIF2B are tuned by P-eIF2alpha concentration.

154 We now report that ISRIB is an activator of eIF2B.

155 ased guanine nucleotide exchange activity of eIF2B is a hallmark of the 'canonical' integrated stress

156 translation through differential activity of eIF2B mediated by protein phosphatase 1.

157 The guanine nucleotide exchange activity of eIF2B plays a key regulatory role in the translation ini

158 the guanine nucleotide exchange activity of eIF2B, whereas phosphorylation by casein kinase II or pr

159 using an increase in the binding affinity of eIF2B for eIF2.

160 it did cause an increase in the affinity of eIF2B for eIF2.

161 However, steady-state kinetic analysis of eIF2B-catalyzed nucleotide exchange revealed that the ab

162 er51 phosphorylation impaired the binding of eIF2B to phosphorylated eIF2alpha.

163 a-subunit of eIF2 did not promote binding of eIF2B to the isolated subunit.

164 ts implicate a defined cytoplasmic center of eIF2B in the exchange of guanine nucleotides on the eIF2

165 he first structural model for the complex of eIF2B with its substrate, eIF2-GDP, reaction intermediat

166 the formation of a novel trimeric complex of eIF2B.

167 Since control of eIF2B is independent of mTOR, these data indicate the op

168 cial for full activity and proper control of eIF2B.

169 nding of eIF2alpha to the regulatory core of eIF2B comprised of the eIF2B alpha, beta and delta subun

170 A focused core of eIF2B guanine nucleotide exchange might allow either gre

171 that eIF2B is actually decameric, a dimer of eIF2B(betagammadeltaepsilon) tetramers stabilized by 2 c

172 together constitute the catalytic domain of eIF2B.

173 Dysregulation of eIF2B activity is associated with a number of pathologie

174 eIF5 GDI complex and determine the effect of eIF2B on this release.

175 We demonstrate that expression of eIF2B mutants lacking the GSK-3beta phosphorylation or p

176 Failure of eIF2B to sense eIF2 phosphorylation likely leads to unre

177 eIF2B and producing the four-subunit form of eIF2B that is less sensitive to eIF2(alphaP).

178 otal role for eIF2Bdelta in the formation of eIF2B(betagammadeltaepsilon) tetramers.

179 Both the five- and four-subunit forms of eIF2B exhibit similar rates of guanine nucleotide exchan

180 ionation experiments show that a fraction of eIF2B cofractionates with lipid membranes in a YBR159W-i

181 the guanine nucleotide exchange function of eIF2B all inhibit eIF2 shuttling into the foci.

182 2, gcd11-K250R, which mimics the function of eIF2B in vitro.

183 ; however, it did suppress the impairment of eIF2B caused by the gcn3c-R104K mutation.

184 The inactivation of eIF2B not only suppresses the initiation of protein tran

185 nd GCN3 that reduce or abolish inhibition of eIF2B activity by eIF2 phosphorylated on its alpha subun

186 (i) a novel mechanism for the inhibition of eIF2B activity, whereby eIF2alpha phosphorylation destab

187 eIF2(alphaP) and mediates the inhibition of eIF2B activity.

188 Since we show that inhibition of eIF2B also drives neural crest migration and yeast invas

189 subcomplex is crucial for the inhibition of eIF2B and attendant downregulation of protein synthesis

190 ensable regulatory role in the inhibition of eIF2B by eIF (alphaP).

191 y subunit GCD7 that eliminated inhibition of eIF2B by eIF2(alphaP) also impaired binding of phosphory

192 the protein into a competitive inhibitor of eIF2B by causing an increase in the binding affinity of

193 onverts eIF2 into a competitive inhibitor of eIF2B, which triggers the integrated stress response (IS

194 F2 x GDP from a substrate to an inhibitor of eIF2B.

195 s eIF2 from a substrate into an inhibitor of eIF2B.

196 sis, we have investigated the involvement of eIF2B, which is inhibited as a result of GSK-3beta phosp

197 We examined the levels of eIF2B subunits in a panel of different mouse tissues and

198 e tissues and identified different levels of eIF2B subunits, particularly eIF2Balpha, which implies h

199 obably because they contain higher levels of eIF2B, the initiation factor that is inhibited by eIF2al

200 MS and cross-linking of eIF2B complexes allows us to propose a model for the sub

201 Through studying the localization of eIF2B subunits, we identified cytoplasmic eIF2B bodies i

202 subcomplex did not compensate for a loss of eIF2B function by mutation and in fact lowered eIF2B act

203 hermodynamics to elucidate the mechanisms of eIF2B action and its regulation by phosphorylation of th

204 arch, the underlying molecular mechanisms of eIF2B action and regulation remain unknown.

205 obal protein synthesis through modulation of eIF2B activity.

206 ranslation resulting from phosphorylation of eIF2B by GSK-3beta thus appears to contribute to the con

207 of 43.2 pmol of GDP released per min/pmol of eIF2B at 30 degrees C is approximately 1 order of magnit

208 heterogeneity in the cellular proportions of eIF2B(alphabetagammadeltaepsilon) and eIF2B(betagammadel

209 hree proteins are critical for regulation of eIF2B by eIF2(alphaP).

210 advances in the understanding of the role of eIF2B as a cause of a common leukodystrophy syndrome.

211 ted eIF2alpha interacts with a subcomplex of eIF2B formed by the three regulatory subunits alpha/GCN3

212 ouble point mutation in the delta-subunit of eIF2B has been identified that results in insensitivity

213 directly to eIF5 and the epsilon subunit of eIF2B, and we map the interaction sites to the catalytic

214 activity of the catalytic epsilon-subunit of eIF2B.

215 eIF5 and the catalytic (epsilon) subunit of eIF2B.

216 mutations in the beta and delta subunits of eIF2B (encoded by GCD7 and GCD2, respectively).

217 idence that the alpha- and delta-subunits of eIF2B are involved in mediating the effect of substrate

218 ate the alpha-, beta-, and delta-subunits of eIF2B in mediating the inhibition by substrate phosphory

219 r the isolated delta- or epsilon-subunits of eIF2B was shown to be located within approximately 70 am

220 d only to the delta- and epsilon-subunits of eIF2B, and eIF2B was shown to bind only to the beta-subu

221 gs of the alpha, beta, and delta subunits of eIF2B.

222 undle domains of delta and alpha subunits of eIF2B.

223 to antagonistic allostery in ISRIB action on eIF2B, culminating in inhibition of the ISR.

224 ion of the ISR and its stimulatory effect on eIF2B GEF activity toward its substrate, the translation

225 ilon (eIF2Bepsilon being the catalytic one), eIF2B has always been considered an alphabetagammadeltae

226 as been reported to directly bind to eIF5 or eIF2B.

227 rred independent of similar changes in other eIF2B subunits.

228 eIF2Bvarepsilon mutations, but not other eIF2B mutations, enhance the ability of overexpressed eI

229 truncated GCD2 protein interacted with other eIF2B subunits only when GCD7 and GCN3 were overexpresse

230 We propose a new model to place eIF2B GDF function in the context of efficient eIF2 recy

231 e show that the catalytic domain can provide eIF2B biological function in vivo when elevated levels e

232 we have coexpressed the five subunits of rat eIF2B in Sf9 cells using the baculovirus system and have

233 GDI and alters cellular responses to reduced eIF2B activity, including control of GCN4 translation.

234 This enables cells to grow with reduced eIF2B GEF activity but impairs activation of GCN4 target

235 ession of a specific isoform of a regulatory eIF2B subunit, eIF2Bdelta variant 1 (V1).

236 ubunit of eIF2 (eIF2alpha), which sequesters eIF2B to prevent exchange activity.

237 at a faster rate compared with five-subunit eIF2B.

238 e also expressed and purified a four-subunit eIF2B complex lacking the alpha-subunit.

239 igodendrocytes during development suppressed eIF2B activity and reproduced the characteristic feature

240 provide evidence that fusel alcohols target eIF2B in order to bring about translational regulation.

241 bind distinct sites in their common target, eIF2B, a guanine nucleotide exchange factor for eIF2.

242 Although it is generally accepted that eIF2B is a pentamer of five non-identical subunits (alph

243 h with purified proteins we demonstrate that eIF2B binds to eIF2 with equal affinity irrespective of

244 We demonstrate that eIF2B has a second activity as a GDI displacement factor

245 ion of alpha-actin and SM22, indicating that eIF2B is required for GSK-3beta-mediated airway smooth m

246 Our data reveal that eIF2B is actually decameric, a dimer of eIF2B(betagammad

247 We show that eIF2B can compete with Met-tRNAi for eIF2-GTP and can de

248 subunits (alpha-epsilon), here we show that eIF2B is a decamer.

249 ght a relationship between body size and the eIF2B subunits localizing to them; larger bodies contain

250 The binding site on eIF2beta for either the eIF2B holoprotein, or the isolated delta- or epsilon-sub

251 EIF2B1 (encoding the eIF2B complex alpha subunit) was the only gene with nove

252 roduct, TC, with direct implications for the eIF2B catalytic mechanism.

253 All five sites are phosphorylated in the eIF2B complex in vivo.

254 in the interactions between subunits in the eIF2B complex.

255 cd7 subunits function with alpha/Gcn3 in the eIF2B regulatory subcomplex that mediates tight, inhibit

256 Mutations in SUI2 and in the eIF2B regulatory subunit GCD7 that eliminated inhibition

257 eIF2alpha phosphorylation inactivates the eIF2B complex.

258 (alphaP) can be decreased by deletion of the eIF2B alpha subunit (encoded by GCN3) and by point mutat

259 he regulatory core of eIF2B comprised of the eIF2B alpha, beta and delta subunits.

260 tory interaction prevents association of the eIF2B catalytic subcomplex with the beta and gamma subun

261 dulation of the phosphorylation state of the eIF2B epsilon-subunit, because deprivation of either ami

262 Gcd1p forms part of the eIF2B guanine nucleotide complex that is responsible for

263 n aIF2B was used to construct a model of the eIF2B regulatory subcomplex.

264 rts eIF2 into a competitive inhibitor of the eIF2B-catalyzed exchange reaction.

265 he extension of the clinical features of the eIF2B-related disorders to encompass both infant- and ad

266 We propose that these variants render the eIF2B complex insensitive to eIF2 phosphorylation, which

267 The structures reveal that the eIF2B decamer is a static platform upon which one or two

268 hione S-transferase [GST]-SUI2) bound to the eIF2B regulatory subcomplex in vitro, in a manner stimul

269 tight binding of phosphorylated SUI2 to the eIF2B regulatory subcomplex is crucial for the inhibitio

270 eIF2(alphaP) holoprotein for binding to the eIF2B regulatory subcomplex.

271 ed binding of phosphorylated GST-SUI2 to the eIF2B regulatory subunits.

272 for achieving correct stoichiometry of these eIF2B subunits in the cell.

273 d sites of regulatory mutations in the three eIF2B subunits in yeast are juxtaposed in one continuous

274 40S ribosomal subunit were assessed through eIF2B activity and eIF2 alpha phosphorylation on Ser-51.

275 Thus, eIF2B-catalyzed TC formation appears to be fine-tuned by

276 Phosphorylation of Ser51 enhances binding to eIF2B through direct interactions of phosphate groups wi

277 cd7 and eIF2alpha all impair eIF2 binding to eIF2B without reducing epsilon/Gcd6 abundance in the nat

278 erved between eIF2 and eIF2alphaP binding to eIF2B, suggesting that the higher affinity of eIF2alphaP

279 t of eIF2 is directly involved in binding to eIF2B.

280 reciprocally opposed each other's binding to eIF2B.

281 ng the phosphorylation site), which binds to eIF2B directly.

282 ctron microscopy structures of eIF2 bound to eIF2B in the dephosphorylated state.

283 eIF2 localizes to eIF2B bodies and shuttles within these bodies in a manne

284 ecamers show greater binding to eIF2 than to eIF2B(betagammadeltaepsilon) tetramers, which may underl

285 nucleotide-exchange activity than wild-type eIF2B that is not inhibited by eIF2(alphaP).

286 Unlike wild-type eIF2B, eIF2B complexes with mutated GCN3 or GCD7 subunit

287 was very rapid and no longer dependent upon eIF2B.

288 Indeed eIF2 shuttles into these foci whereas eIF2B remains largely resident.

289 While eIF2B contains five subunits, the epsilon/Gcd6 subunit i

290 wo flexible eIF2 trimers bind and align with eIF2B's bipartite catalytic centers to catalyze nucleoti

291 complex (MFC), while eIF2GDP associates with eIF2B for guanine nucleotide exchange.

292 ence that aIF2B has functions in common with eIF2B, the crystal structure established for an aIF2B wa

293 hese bodies in a manner that correlates with eIF2B activity.

294 and p-eIF2 differ in their interaction with eIF2B to such effect that p-eIF2-eIF2B association can b

295 a model for the subunit arrangements within eIF2B where the subunit assembly occurs through catalyti

296 ubunit stoichiometry and interactions within eIF2B and eIF2.

297 ve determined the cryo-EM structure of yeast eIF2B in complex with phosphorylated eIF2 at an overall

298 In support of this model, our yeast eIF2B preparations bind guanine nucleotides, with an app

299 We have purified yeast eIF2B and characterized its catalytic properties in vitr

300 -exchange assay to show that wild-type yeast eIF2B is inhibited by phosphorylated eIF2 [eIF2(alphaP)]