ライフサイエンスコーパス: cotranslational

1 iling to define the principles governing the cotranslational action of the chaperones TRiC/CCT and Hs

2 t the turn motif (TM) site, Thr450, to avoid cotranslational Akt ubiquitination.

3 exes STT3A-OST and STT3B-OST, which catalyze cotranslational and post-translational N-glycosylation,

4 Here we identify cotranslational and posttranslational folding intermedia

5 ed glycosylation of proteins is an essential cotranslational and posttranslational protein modificati

6 IGNAL RECOGNITION PARTICLE54) is involved in cotranslational and posttranslational sorting of thylako

7 Atp9-Oxa1 interaction is in contrast to the cotranslational and transient interaction previously obs

8 that this direct integration is obligatorily cotranslational, and by synthesizing stable ribosome-bou

9 SecY translocon complex is required for the cotranslational assembly of membrane proteins in bacteri

10 ty that this sequence feature may aid in the cotranslational assembly of ribosomes by delaying the re

11 n the course of mRNA translation, suggesting cotranslational assembly of the ZNF277-uS5 complex.

12 tably, loss of SSB dramatically enhances the cotranslational association of SSA with nascent chains,

13 d effectively as a CALI chromophore, and its cotranslational attachment to the target protein avoids

14 e particularly relevant to the synthesis and cotranslational behavior of some proteins.

15 ation of D1 protein turnover by facilitating cotranslational biosynthesis insertion (C-terminal domai

16 c-mediated transport and works best when the cotranslational branch of the pathway is employed.

17 ate that the profolding role of Hsc70 during cotranslational CFTR folding is counterbalanced by a dom

18 Because CFTR folding is predominantly cotranslational, changes in translational dynamics may p

19 ides are accurately sorted between the major cotranslational chaperone trigger factor (TF) and the es

20 ress this question by studying the role of a cotranslational chaperone, nascent polypeptide-associate

21 s and of the canonical sequence required for cotranslational cleavage resembled the genetic organizat

22 For type II membrane proteins, these cotranslational constraints include N- and C-terminal me

23 egradome data demonstrated RRGD loci undergo cotranslational decay and identified changes in the ribo

24 ly(A(+)) mRNA targets are largely subject to cotranslational decay during plant development.

25 Our approach allowed the determination of a cotranslational decay efficiency that could be an altern

26 f transcripts were specifically subjected to cotranslational decay in a developmental-dependent manne

27 g complex, reveal a role for this protein in cotranslational decay.

28 This pattern of cotranslational degradation is especially evident near t

29 ubiquitylation has been suggested to signal cotranslational degradation of nascent polypeptides, cot

30 Cotranslational degradation of polypeptide nascent chain

31 alpha) is required for ubiquitin-independent cotranslational degradation of the transcription factor

32 ic ribosome-associating factor that triggers cotranslational degradation of tubulin mRNAs in response

33 The disruption of core glycosylation, a cotranslational event, allows us to pinpoint these N-ter

34 n maturation process and shows how important cotranslational events contribute to the proper cellular

35 pid folding of thioredoxin in the cytoplasm; cotranslational export by the DsbA signal sequence avoid

36 Oxa1 is known to be required for cotranslational export of the Cox2 N-terminal domain acr

37 3 and the previously described selenoprotein cotranslational factors resulted in a model of selenocys

38 By combining S-acylation and cotranslational fatty acid chemical reporters with ortho

39 ses associated with protein biosynthesis and cotranslational folding (CTF).

40 iates predicted by a native-centric model of cotranslational folding account for the majority of thes

41 hether conformational constraints imposed by cotranslational folding affect the partitioning between

42 kinetics which reduces their probability of cotranslational folding and consequently increases the n

43 ain III on its C-terminal neighbors disrupts cotranslational folding and imposes a posttranslational

44 nonymous polymorphism, affects the timing of cotranslational folding and insertion of P-gp into the m

45 Hsp70 functions in both the cotranslational folding and posttranslational degradatio

46 e we present a kinetic formalism to describe cotranslational folding and predict the effects of varia

47 nced understanding of the molecular basis of cotranslational folding at atomic resolution.

48 The same effect is achieved by cotranslational folding at the ribosome in vivo.

49 Specifically, we investigate how the cotranslational folding behavior of the R15 and R16 doma

50 in (RNC) complex is the major determinant of cotranslational folding behavior.

51 nslation rates can reduce the probability of cotranslational folding below that associated with arres

52 We tested whether this cotranslational folding can alter the folded structure o

53 The vectorial (N- to C-terminal) nature of cotranslational folding constrains the conformations of

54 Moreover, restoration of the NBD1 cotranslational folding defect by second site suppressor

55 nts in order to evaluate the extent to which cotranslational folding defects influence membrane prote

56 Cotranslational folding depends on the folding speed and

57 The majority of these cotranslational folding domains are influenced by transl

58 r proteins are predicted not to benefit from cotranslational folding due to a lack of significant non

59 conditions, such a slowdown indeed improves cotranslational folding efficiency by giving these nasce

60 ar proteins while directly measuring initial cotranslational folding forces.

61 fusion protein, we demonstrate an efficient cotranslational folding immediately after the emergence

62 slowly translated codons are associated with cotranslational folding intermediates, which may be smal

63 a coli genes and associated such codons with cotranslational folding intermediates.

64 vitro system that allows direct analysis of cotranslational folding intermediates.

65 ontrast to refolding of a denatured protein, cotranslational folding is complicated by the vectorial

66 Thus, cotranslational folding is predicted to be beneficial be

67 Our perspective is that cotranslational folding is the norm, but that the effect

68 integrated cellular response that shapes the cotranslational folding landscape at critical stages of

69 Cotranslational folding may be typical of small, intrins

70 Cotranslational folding mechanisms are therefore linked

71 es, and the ability to investigate real-time cotranslational folding of a polypeptide.

72 mal mRNA sequences to control the simulated, cotranslational folding of a protein in a user-prescribe

73 Here, we study the cotranslational folding of adjacent domains from the cyt

74 Achieving efficient cotranslational folding of complex proteomes poses a cha

75 sociated cotranslational sequencing to track cotranslational folding of hemagglutinin in influenza A

76 equences evolved to fold in cells, including cotranslational folding of nascent polypeptide chains du

77 ur fixed lengths in vivo, in order to assess cotranslational folding of newly synthesized tailspike c

78 ich sequences act as "tRNA sponges" and help cotranslational folding of parasite proteins.

79 ation and open up possibilities to study the cotranslational folding of polytopic membrane proteins.

80 otein, modulate the rates of translation and cotranslational folding of protein domains monitored in

81 scence resonance energy transfer, we studied cotranslational folding of the first nucleotide-binding

82 rk, we show that the forces generated by the cotranslational folding of the nascent polypeptide chain

83 Our observations show that cotranslational folding of the protein, which folds auto

84 Together, our results indicate that cotranslational folding of this viral protein generates

85 cate an inverse correlation between CTPD and cotranslational folding on a proteome scale.

86 ediated translational recoding, a variety of cotranslational folding or binding events may also stimu

87 lationship between translation speed and the cotranslational folding probability is a general phenome

88 erone network likely underlies the elaborate cotranslational folding process necessary for the evolut

89 c formalism that we discuss can describe the cotranslational folding process occurring on a single ri

90 ing lengths, simulating intermediates in the cotranslational folding process.

91 tional design of mRNA sequences to guide the cotranslational folding process.

92 Ribosome-associated chaperones and cotranslational folding protect the majority of nascent

93 generality of fitness effects resulting from cotranslational folding remain open questions.

94 whose intrinsic properties hinder efficient cotranslational folding remain susceptible for cotransla

95 an intermediate or misfold, and examine the cotranslational folding scenarios that are possible with

96 We also determine possible cotranslational folding sites initiated by hydrophobic c

97 ctrum of nascent protein behaviors including cotranslational folding, aggregation, and translocation.

98 omputationally the existence of evidence for cotranslational folding, based on large sets of experime

99 n diverse functions, including regulation of cotranslational folding, covalent modifications, secreti

100 model and provide a molecular perspective on cotranslational folding, misfolding, and the impact of t

101 Escherichia coli cytosolic proteins exhibit cotranslational folding, with at least one domain in eac

102 and slow translation rates hinder efficient cotranslational folding.

103 s in facilitating polypeptide elongation and cotranslational folding.

104 how native structure influences evolution of cotranslational folding.

105 force on the nascent chain of ~15 pN during cotranslational folding.

106 chains, including related phenomena such as cotranslational folding.

107 slation speeds at certain positions enhances cotranslational folding.

108 he hierarchical action of Hsp70 and TRiC for cotranslational folding.

109 have evolved to maximize their fitness with cotranslational folding.

110 eins with local contact topologies to evolve cotranslational folding.

111 lly important as pause sites in coordinating cotranslational folding.

112 overs evidence of evolutionary selection for cotranslational folding.

113 AT ectodomain, with the initial and probably cotranslational formation of Cys-242-Cys-273, followed b

114 The STT3B isoform is required for efficient cotranslational glycosylation of an acceptor site adjace

115 T3A OST isoform is primarily responsible for cotranslational glycosylation of the nascent polypeptide

116 the protein translocation channel to mediate cotranslational glycosylation, while the STT3B complex c

117 mer and for its allosteric regulation during cotranslational glycosylation.

118 The proposed tentative paths of cotranslational helix assembly of several polytopic prot

119 in the mouse embryo through mTORC2-catalyzed cotranslational IMP1/IMP3 phosphorylation.

120 rotein synthesis, but direct evidence of its cotranslational incorporation is currently lacking.

121 and flash photolysis measurements after its cotranslational insertion into nanodiscs.

122 acting on transmembrane helices during their cotranslational insertion into the inner membrane of Esc

123 From the moment of cotranslational insertion into the lipid bilayer of the

124 erally thought to be determined during their cotranslational insertion into the membrane.

125 It is more effective in cotranslational insertion of membrane proteins and the p

126 Cotranslational insertion of membrane proteins into defi

127 hyll biosynthesis and the Sec/YidC-dependent cotranslational insertion of nascent photosystem polypep

128 eats, postulated to facilitate the psbA mRNA cotranslational insertion of the nascent D1 protein in t

129 Cotranslational insertion of the nascent peptide into th

130 drops may provide a hydrophobic interior for cotranslational insertion of the transmembrane helices a

131 TMDs (DeltaG(app) > 0 kcal/mol) require the cotranslational insertion process for facilitating their

132 are occupied by translating ribosomes during cotranslational insertion, impeding the translocation of

133 During cotranslational integration of a eukaryotic multispannin

134 t links ribosomes to thylakoid membranes for cotranslational integration.

135 ernately into the cytosol or ER lumen during cotranslational integration.

136 toward a comprehensive understanding of the cotranslational interactions of nascent chains, which pa

137 chaperone trigger factor delays the onset of cotranslational interactions until the LuxB dimer interf

138 We describe here a technology, based on the cotranslational introduction of azide groups into protei

139 Overall the cotranslational inversion of marginally hydrophobic NA T

140 protein domains, allowing them to fold in a cotranslational-like sequential process.

141 dly modifies newly synthesized proteins in a cotranslational manner.

142 exit site such that integration occurs in a cotranslational manner.

143 Here, we characterized the cotranslational maturation pathway for the human type I

144 The cotranslational maturation process for the type II membr

145 nto operons therefore reflects a fundamental cotranslational mechanism for spatial and temporal regul

146 bacterial plasma membrane in an obligatorily cotranslational mechanism.

147 s is consistent with the vectorial nature of cotranslational membrane insertion found in vivo.

148 dase (COX) complex, where it facilitates the cotranslational membrane insertion of mitochondrially en

149 doplasmic reticulum (ER), where they undergo cotranslational membrane integration and assembly.

150 cross-link with Sf9 importin-alpha-16 during cotranslational membrane integration and remain proximal

151 that protein topology is established during cotranslational membrane integration.

152 as a central element in early initiation of cotranslational membrane targeting.

153 at the I507-ATC-->ATT SCC contributes to the cotranslational misfolding, ERAD, and to the functional

154 bally slowed down, possibly due to increased cotranslational misfolding.

155 The cotranslational mixed-disulfide intermediate is, upon fu

156 For mitochondria, a cotranslational model of protein import is now proposed

157 one of the limited examples of post- and/or cotranslational modification of proteins in this unusual

158 Cotranslational modification of the proteins by FGE prod

159 t two amino acids on proteins is a prevalent cotranslational modification.

160 ase A (PKA-C) is subject to several post- or cotranslational modifications that regulate its activity

161 s approach to reveal the global landscape of cotranslational mRNA decay during Arabidopsis (Arabidops

162 Cotranslational mRNA decay globally shapes the transcrip

163 s, our results demonstrate the prevalence of cotranslational mRNA decay in plant development and its

164 ranscripts to reveal the global landscape of cotranslational mRNA decay in the Arabidopsis thaliana t

165 As cotranslational mRNA decay is interconnected with transl

166 We demonstrated that cotranslational mRNA decay is regulated by developmental

167 ic to translation, discovery of the 5' to 3' cotranslational mRNA decay pathway demonstrated that bot

168 Cotranslational mRNA degradation is initiated by decappi

169 is defective in cystic fibrosis, folds via a cotranslational multistep pathway as it is synthesized o

170 Cotranslational N-glycosylation by the STT3A isoform of

171 Cotranslational N-glycosylation can accelerate protein f

172 ligosaccharyl transferase (OT) catalyzes the cotranslational N-glycosylation of nascent polypeptides

173 y sensitive to pharmacological inhibition of cotranslational N-glycosylation.

174 nopeptidase (MetAP) carries out an important cotranslational N-terminal methionine excision of nascen

175 p among a protein's amino acid sequence, its cotranslational nascent-chain elongation rate, and foldi

176 el derived from the data accurately predicts cotranslational NME efficiency in the cytosol.

177 entified proteins and further validate their cotranslational O-GlcNAcylation.

178 We propose a model for cotranslational oxidative folding wherein PDI acts as a

179 targeting polypeptides for secretion via the cotranslational pathway.

180 llosteric agonist NPS R-568, which acts as a cotranslational pharmacochaperone.

181 Cotranslational presence of MTP can dramatically promote

182 nto the membrane does not occur via a simple cotranslational process.

183 approaches have been combined to understand cotranslational processes at multiple scales, and the ne

184 this review, we discuss recent insights into cotranslational processes gained from molecular simulati

185 Cotranslational processes involving a nascent protein in

186 anifestation of the nonequilibrium nature of cotranslational processes, and as such, there exist theo

187 nection between the nonequilibrium nature of cotranslational processes, nascent-protein behavior, and

188 products identical to those observed during cotranslational processing of the authentic ORF1 polypro

189 As a consequence, different cotranslational profiles of the same protein can have di

190 vity, and provides a platform to study other cotranslational protein biogenesis pathways.

191 They facilitate cotranslational protein complex formation, which establi

192 This process, called cotranslational protein degradation (CTPD), has been obs

193 previously unknown role for Srp1 and Sts1 in cotranslational protein degradation and suggests a novel

194 We further demonstrate that cotranslational protein degradation is generally impaire

195 Cotranslational protein degradation plays an important r

196 FPA and PET-FCS in solving the trajectory of cotranslational protein folding and in characterizing th

197 How cotranslational protein folding and the rate of synthesi

198 function to regulate protein translation and cotranslational protein folding and to target and degrad

199 ict that fast-translating codons can enhance cotranslational protein folding by helping to avoid misf

200 air cell fitness by significantly perturbing cotranslational protein folding mechanisms, despite the

201 Cotranslational protein folding requires assistance from

202 along a transcript, have been shown to alter cotranslational protein folding, suggesting that evoluti

203 translated can increase their probability of cotranslational protein folding, while speeding up codon

204 age "code" within genetic codons to regulate cotranslational protein folding.

205 t as slow-translating codons in coordinating cotranslational protein folding.

206 rotein biosynthesis is inherently coupled to cotranslational protein folding.

207 h interfering with translation kinetics, and cotranslational protein folding.

208 Cotranslational protein maturation is often studied in c

209 N-Linked glycosylation is a common cotranslational protein modification that can regulate p

210 nderstanding the roles of O-GlcNAc and other cotranslational protein modifications and should stimula

211 esent results indicate that mTORC2-catalyzed cotranslational protein phosphorylation is a core functi

212 ses Hsf1 monitors and elucidates a conserved cotranslational protein quality control mechanism.

213 cribes how these features may play a role in cotranslational protein quality control.

214 ns, eukaryotic release factors contribute to cotranslational protein quality control.

215 During cotranslational protein targeting by the signal recognit

216 An example of such control occurs in cotranslational protein targeting by the signal recognit

217 Cotranslational protein targeting by the signal recognit

218 Cotranslational protein targeting delivers proteins to t

219 Cotranslational protein targeting is a conserved process

220 embly, signal recognition particle-dependent cotranslational protein targeting to membrane, and mRNA

221 Cotranslational protein targeting to membranes is regula

222 ssential role in sensing the ribosome during cotranslational protein targeting to the endoplasmic ret

223 During cotranslational protein targeting, two guanosine triphos

224 P activity are essential for the fidelity of cotranslational protein targeting.

225 ves as docking sites for both TF and SRP, in cotranslational protein targeting.

226 n particle (SRP) is universally required for cotranslational protein targeting.

227 some to activate SRP-SR assembly and impairs cotranslational protein targeting.

228 al time for recognition by the machinery for cotranslational protein translocation into the ER.

229 hat this modification plays a direct role in cotranslational protein translocation into the ER.

230 Cotranslational protein translocation is a universally c

231 broad outer-membrane defects and premature, cotranslational protein translocation.

232 xtent to which nascent chains are subject to cotranslational quality control and degradation remains

233 Therefore, cells evolved cotranslational quality control mechanisms that eliminat

234 hese results suggest that CaSR is subject to cotranslational quality control, which includes a pharma

235 ns in budding yeast has been assumed to be a cotranslational reaction.

236 However, in contrast to the canonical cotranslational recognition by SRP, SRP was found to bin

237 Moreover, cotranslational recruitment of both TRiC and Hsp70 corre

238 chanisms act in concert to promote efficient cotranslational recruitment.

239 Moreover, excess TF interferes with cotranslational removal of the N-terminal formyl methion

240 Their cotranslational rerouting to the cytosol for degradation

241 bosome stalling on eukaryotic mRNAs triggers cotranslational RNA and protein degradation through cons

242 strate the global prevalence and features of cotranslational RNA decay in a plant transcriptome.

243 nalysis in xrn4 mutant plants indicates that cotranslational RNA decay is XRN4 dependent.

244 ated by a viral peptide sequence that causes cotranslational scission of emerging peptide chains.

245 we present an engineered system for specific cotranslational Sep incorporation (directed by UAG) into

246 present a strategy called folding-associated cotranslational sequencing that enables monitoring of th

247 We also apply folding-associated cotranslational sequencing to track cotranslational fold

248 oplasmic reticulum via an alternative to the cotranslational, signal recognition particle-dependent m

249 relevant to cpSRP54's role in the post- and cotranslational signaling processes.

250 aminoacyl-tRNA synthetase/tRNA pair for the cotranslational, site-specific incorporation of two unna

251 Here, we report the dispensability of the cotranslational SRP protein translocation system in a ba

252 "2A-like" sequence element that specifies a cotranslational "stop/continue" event releasing the exog

253 The early elongation pausing represents a cotranslational stress response to maintain the intracel

254 sensitive and global approach to define the cotranslational substrate specificity of the yeast Hsp70

255 lves spatially confined, actively chaperoned cotranslational subunit interactions.

256 C-terminus, underscores the contribution of cotranslational synthesis to TMD inversion.

257 lly thought to occur via two major pathways: cotranslational targeting by signal recognition particle

258 perone trigger factor (TF) and the essential cotranslational targeting machinery, signal recognition

259 Our results demonstrate that cotranslational targeting of a protein to the E. coli Se

260 ed protein targeting machine and mediate the cotranslational targeting of inner membrane proteins to

261 Cotranslational targeting of membrane proteins is mediat

262 y is achieved in one of these processes, the cotranslational targeting of nascent membrane and secret

263 icle (SRP) and SRP receptor (SR) mediate the cotranslational targeting of proteins to cellular membra

264 e major cellular machinery that mediates the cotranslational targeting of proteins to cellular membra

265 subunit (cpSRP54) is required for efficient cotranslational targeting of several central photosynthe

266 a molecular description of the SecA-mediated cotranslational targeting pathway and demonstrates an un

267 on of Sbh1p and Sbh2p causes a defect in the cotranslational targeting pathway that is similar to the

268 y mimicking the effect of the SRP RNA in the cotranslational targeting pathway.

269 the N-terminal extension, however, restored cotranslational targeting.

270 ligosaccharyltransferase (OST) catalyzes the cotranslational transfer of high-mannose sugars to nasce

271 sting data and our findings, we propose that cotranslational translocation and N-glycosylation of nas

272 Surprisingly, the slow growth and cotranslational translocation defects caused by deletion

273 Cotranslational translocation defects in the ssh1DeltaSR

274 marine cyanobacteria that act by preventing cotranslational translocation early in the secretory pat

275 slocon component associations during defined cotranslational translocation events.

276 he RQC pathway can also target stalls during cotranslational translocation into the ER is not known.

277 nd raises the possibility that inhibition of cotranslational translocation may be exploited for antic

278 ecludes them from utilizing the well-studied cotranslational translocation mechanism of most transmem

279 Cotranslational translocation of apoB100 across the endo

280 s, we demonstrated that apratoxin A prevents cotranslational translocation of proteins destined for t

281 the DsbA signal sequence promotes efficient, cotranslational translocation of the cytoplasmic protein

282 erates with either a translating ribosome in cotranslational translocation or the SecA ATPase in post

283 ocation of nascent polypeptides that use the cotranslational translocation pathway.

284 sec61 mutants affect different steps in the cotranslational translocation pathway.

285 ve defects in both the posttranslational and cotranslational translocation pathways due to a kinetic

286 e revealed that modulation of Sec61-mediated cotranslational translocation selectively impaired glyco

287 Cotranslational translocation was expected to be ineffic

288 ast, point mutations in L6 of Sec61p inhibit cotranslational translocation without significantly redu

289 the nascent HER3 protein from initiating its cotranslational translocation, resulting in the degradat

290 In cotranslational translocation, the ribosome feeds the po

291 hain domains not only before but also during cotranslational translocation.

292 ration into a cyclodepsipeptide inhibitor of cotranslational translocation.

293 These data show that cotranslational translocon contacts are ultimately contr

294 tially implying a new layer of regulation of cotranslational transport.

295 We report that cotranslational ubiquitination (CTU) is a robust process

296 Here, we directly and quantitatively assess cotranslational ubiquitination and identify, at a system

297 Cotranslational ubiquitination occurs at very low levels

298 translational folding remain susceptible for cotranslational ubiquitination.

299 ational degradation of nascent polypeptides, cotranslational ubiquitylation occurs at a low level, su

300 reaction and that the mode of translocation (cotranslational verse posttranslational) can affect the