ライフサイエンスコーパス: prefusion

1 the full-length S protein, representing its prefusion (2.9-angstrom resolution) and postfusion (3.0-

2 ractions are cooperative, and binding to the prefusion acceptor t-SNARE complex is stronger than to t

3 secondary and tertiary structure between the prefusion and hairpin conformations regulate F protein e

4 he structural changes that occur between the prefusion and postfusion conformations of the fusion pro

5 protein adopts before and after virus entry (prefusion and postfusion conformations, respectively).

6 ture, and structural differences between its prefusion and postfusion conformations, we hypothesized

7 RSV-neutralizing epitopes shared between the prefusion and postfusion conformations.

8 on pathway have been postulated based on the prefusion and postfusion crystal structures of the viral

9 Crystal structures of both prefusion and postfusion forms have illuminated the conf

10 ent assay (ELISA) using soluble forms of the prefusion and postfusion forms of the F protein as targe

11 alization titers, anti-F binding antibodies (prefusion and postfusion proteins), antibody avidity, an

12 Key neutralization epitopes of prefusion and postfusion RSV F have been identified, and

13 We also included stabilized versions of prefusion and postfusion RSV F protein.

14 ed a large conformational change between the prefusion and postfusion states, suggesting that postfus

15 then compared vectors expressing stabilized prefusion and postfusion versions of RSV F.

16 in two structurally distinct conformations, prefusion and postfusion.

17 f F have been described: monomeric, trimeric prefusion, and trimeric postfusion.

18 abling multivalent display of F trimers with prefusion antigenicity.

19 mplex would stabilize BG505 SOSIP.664 in its prefusion closed conformation and limit reactivity to we

20 To stabilize the trimer in its prefusion closed conformation, we complexed trimeric BG5

21 rystal structures of these trimers confirmed prefusion-closed apexes stabilized by hydrophobic patche

22 at stabilize the apex of the Env trimer in a prefusion-closed conformation and show antigenically, st

23 The prefusion-closed conformation of HIV-1 Env has been iden

24 IV-1 envelope (Env) trimers, stabilized in a prefusion-closed conformation, can elicit humoral respon

25 lize BG505 DS-SOSIP in the vaccine-preferred prefusion-closed conformation.

26 by vaccine boosting of these responses with prefusion-closed Env trimers.

27 conformation of the HIV-1 Env trimer to its prefusion-closed state as this state is recognized by mo

28 which stabilizes Env in the vaccine-desired prefusion-closed state.

29 terface of potentially mobile domains of the prefusion-closed structure.

30 litates virus entry by transitioning between prefusion-closed, CD4-bound, and coreceptor-bound confor

31 e a straightforward method to trap and study prefusion complexes on native membranes, and reveal that

32 l-atom molecular-dynamics simulations of the prefusion configuration of synaptobrevin in a lipid bila

33 tein engineered to preferentially maintain a prefusion conformation (RSV-PreF vaccine) or placebo.

34 accine engineered to preferentially maintain prefusion conformation (RSV-PreF), 128 healthy men 18-44

35 ons of these viral glycoproteins, the native prefusion conformation and a receptor-induced metastable

36 irus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineer

37 on (F) glycoprotein trimer-stabilized in the prefusion conformation and fused with SpyCatcher-could b

38 form, important mechanistic aspects of this prefusion conformation and its lipid interactions, befor

39 scopy structure of the PEDV S protein in the prefusion conformation at a resolution of 3.1 angstrom.

40 irus GPs tested suffered a concerted loss of prefusion conformation at elevated temperatures but did

41 membrane fusion and the apparent loss of the prefusion conformation at neutral pH.

42 lternative strategies to arrest RSV F in the prefusion conformation based on the prevention of hinge

43 ion protein (RSV F) stabilized in the native prefusion conformation has been described.

44 F mutants stabilized in the prefusion conformation interact with H intracellularly a

45 ion process F is converted from a metastable prefusion conformation into an energetically favored pos

46 mutations that stabilize the structure in a prefusion conformation may stimulate higher titers of pr

47 f viral membrane fusion by destabilizing the prefusion conformation of EBOV GP.

48 recognize a glycan-dependent epitope on the prefusion conformation of gp41 and unambiguously disting

49 t the trimeric MPER structure represents the prefusion conformation of gp41, preceding the putative p

50 -fragment immunogen which mimics the native, prefusion conformation of HA and binds conformation spec

51 ng as molecular glue, Arbidol stabilizes the prefusion conformation of HA that inhibits the large con

52 The prefusion conformation of HIV-1 envelope protein (Env) i

53 mutations are identified that stabilize the prefusion conformation of RSV F and dramatically increas

54 ave demonstrated that antibodies against the prefusion conformation of RSV F have more potent neutral

55 The prefusion conformation of RSV F is considered the most r

56 he previously described stabilization of the prefusion conformation of the F protein.

57 The prefusion conformation of the HA is metastable, and the

58 teractions are important for stabilizing the prefusion conformation of the protein prior to triggerin

59 Our studies reveal a stable prefusion conformation of the spike immunogen with sligh

60 lar synaptobrevin-2 (syb-2) in its monomeric prefusion conformation shows high flexibility, character

61 F initially folds to a metastable prefusion conformation that becomes activated via a clea

62 dy is not solvent accessible in the compact, prefusion conformation that typifies all HA structures t

63 protein conformational change from the known prefusion conformation to an extended, monomeric interme

64 me triggers a transition from the metastable prefusion conformation to the stable fusion conformation

65 suggests this is the postfusion rather than prefusion conformation, although this is not proven.

66 the RSV fusion (F) antigen, in its post- or prefusion conformation, and in the presence of a Th1-bia

67 ry syncytial virus fusion (F) protein in its prefusion conformation, and we show that the potent nano

68 usion (F) glycoprotein trimer, folded in its prefusion conformation, i.e., before activation for memb

69 a published EBOV-GP crystal structure in its prefusion conformation, suggested a hydrophobic pocket a

70 that leads to release of the B loop from its prefusion conformation, which is aided by unexpected str

71 3C/V484C and V484C/N485C were able to bind a prefusion conformation-specific antibody prior to cell d

72 ds, HeV F can still fold properly and bind a prefusion conformation-specific antibody prior to cell d

73 it F-mediated fusion by stabilizing F in its prefusion conformation.

74 mini-stem folds as a trimer mimicking the HA prefusion conformation.

75 structural mimic of the native trimer in its prefusion conformation.

76 S-CoV-2 full-length spike, stabilized in the prefusion conformation.

77 tructure of micelle-bound syntaxin-1A in its prefusion conformation.

78 ary to establish and maintain the metastable prefusion conformation.

79 Yet, none of the constructs adopted the prefusion conformation.

80 lds the fusion subunit GP2 in its metastable prefusion conformation.

81 oV-2 spike protein that is stabilized in the prefusion conformation.

82 must be partly or transiently exposed in the prefusion conformation.

83 tructures, reveals a breathing motion of the prefusion conformation.

84 y structure of the 2019-nCoV S trimer in the prefusion conformation.

85 vector encoding the F protein stabilized in prefusion conformation.

86 say and negative-stain EM, we found that the prefusion conformational state of LT5.J4b12C trimeric En

87 ynamic, transitioning between three distinct prefusion conformations, whose relative occupancies were

88 How the prefusion conformer transitions to the postfusion confor

89 dependent stability (thermostability) of the prefusion conformers of class I viral fusion glycoprotei

90 ns and synaptic protein complex densities at prefusion contact sites between membranes.

91 sion peptides from their burial sites in the prefusion crystal structure.

92 tructures are strikingly similar in both the prefusion dimer and the postfusion homotrimer conformati

93 near the point of rotation that converts the prefusion dimer to the postfusion state.

94 esent the crystal structure of the trimeric, prefusion ectodomain of Lassa GP bound to a neutralizing

95 The prefusion Env trimer is stabilized by V1V2 loops that in

96 deavor has been our inability to produce the prefusion envelope glycoprotein trimer for biochemical a

97 rticle (VLP)-associated, mutation-stabilized prefusion F (pre-F) proteins, including the prototype DS

98 At high doses, prefusion F also induced the highest titers of neutraliz

99 This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune r

100 rotein forms, reacted predominantly with the prefusion F conformation.

101 t against RSV and why specifically targeting prefusion F could have great clinical potential.

102 cterized by short-range contacts between the prefusion F head and the attachment protein stalk, possi

103 fusion F protein, titers of IgG specific for prefusion F induced by the pre-F/F-containing VLPs were

104 In a hamster model, prefusion F induced increased quantity and quality of RS

105 Although prefusion F induces higher levels of neutralizing antibo

106 Although prefusion F is able to induce high levels of neutralizin

107 Globally, metastable prefusion F is oxidized more extensively than postfusion

108 In all cases, the prefusion F mutant did not induce higher neutralizing an

109 These findings indicate that the prefusion F protein assembled into VLPs has the potentia

110 LP vaccine candidate containing a stabilized prefusion F protein can robustly stimulate protective im

111 of VLPs containing a conformation-stabilized prefusion F protein stimulated high titers of neutralizi

112 bridges to introduce covalent links into the prefusion F protein trimer of measles virus.

113 by VLPs containing different versions of the prefusion F protein varied by 40-fold in the extent of p

114 The S443D mutation destabilizes prefusion F proteins by disrupting a hydrogen bond netwo

115 We showed that alternative versions of prefusion F proteins have different conformations and in

116 rotect mice, larger amounts of monomeric and prefusion F proteins were required for protection.

117 tal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity

118 e resistance mutations lower the barrier for prefusion F triggering, resulting in an accelerated RSV

119 proteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending

120 oprotein; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending

121 chinery; upon receptor engagement by HN, the prefusion F undergoes a structural transition, extending

122 ric form of hRSV F that shares epitopes with prefusion F was recently reported.

123 Antibodies induced by all doses of prefusion F, in contrast to other F protein forms, react

124 on of the three-helix bundle stalk domain of prefusion F, the MPER region also needs to separate for

125 ing pathway, but a detailed understanding of prefusion F-protein metastability remains elusive.

126 During recent years, many prefusion F-specific antibodies have been described.

127 An inhibitory prefusion F-specific sAb recognized a quaternary antigen

128 These prefusion F-specific VHHs represent promising antiviral

129 dies recognize epitopes found exclusively in prefusion F.

130 with more pathology after challenge than was prefusion F.

131 head domain of the attachment protein above prefusion F.

132 t rB/HPIV3 expressing a partially stabilized prefusion form (pre-F) of RSV F efficiently induced "hig

133 ding modifications intended to stabilize the prefusion form and novel mutations aimed at destabilizin

134 ons in which hRSV_F can fold, the metastable prefusion form and the highly stable postfusion conforma

135 ly represents the postfusion form of gB; the prefusion form has not yet been determined.

136 p140 oligomers do not represent an authentic prefusion form of Env, whereas gp140 monomers isolated f

137 oligomeric structure and thus resembled the prefusion form of gB in the virion.

138 results underscore the importance of using a prefusion form of gB to assess the activation and extent

139 crystal structure of the cleavage-activated prefusion form of PIV5 F.

140 rally defined and stabilized versions of the prefusion form of the F glycoprotein and are advancing r

141 rs change in the antigenic reactivity of the prefusion form of the herpes simplex virus (HSV) fusion

142 several approaches aimed at engineering the prefusion form of the herpes simplex virus type 1 gB ect

143 ere, we present the crystal structure of the prefusion form of the HeV F ectodomain.

144 ociation contributes to the stability of the prefusion form of the protein, supporting a role for TM-

145 , consistent with decreased stability of the prefusion form of the protein.

146 Thus, VLPs containing a stabilized prefusion form of the RSV F protein represent a promisin

147 accine as a vector to express a noncleavable prefusion form of the SARS-CoV-2 spike antigen.

148 that HRB forms a trimeric coiled coil in the prefusion form of the whole protein though HRB peptides

149 The prefusion form of these envelope glycoproteins thus repr

150 unique class of antibodies specific for the prefusion form of this protein that account for most of

151 on function by maintaining gB in an inactive prefusion form prior to activation by receptor binding.

152 olds initially to form a trimeric metastable prefusion form that is triggered to undergo large-scale

153 usion loops function as gB transits from its prefusion form to an active fusogen.

154 es together by refolding from its initial or prefusion form to its final or postfusion form.

155 ormational intermediates from the metastable prefusion form to the stable postfusion form.

156 The crystal structure of the F protein (prefusion form) of the paramyxovirus parainfluenza virus

157 intrinsically disordered in their monomeric prefusion form, important mechanistic aspects of this pr

158 sion conformation, but some were also in the prefusion form.

159 een assumed to be mostly unstructured in its prefusion form.

160 re nonfunctional due to being "trapped" in a prefusion form.

161 Structures of prefusion forms of RSV F, as well as other class I fusio

162 n in virions, including the disappearance of prefusion glycoprotein spikes and increased particle dia

163 nducing conformational rearrangements in the prefusion GP trimer that dramatically enhance its suscep

164 terface in the membrane-proximal base of the prefusion GP trimer.

165 mplex, and, ultimately, the structure of the prefusion gp120-gp41 complex.

166 t these small molecules act to stabilize the prefusion GPC complex against acidic pH.

167 istate moiety is cryptically disposed in the prefusion GPC complex and may function late in the fusio

168 n located at the membrane-distal site of the prefusion HA stalk that was also previously suggested as

169 nanoparticles presented antigenically intact prefusion HIV-1 Env, influenza hemagglutinin, and RSV F

170 We found that a prefusion intermediate will assemble with HOPS and the R

171 e postfusion form without first adopting the prefusion intermediate.

172 n determined, any other conformations (e.g., prefusion, intermediate conformations) have so far remai

173 rane association, and probable structures of prefusion intermediates.

174 ggest that the uncleaved RSV F monomer has a prefusion-like conformation and is a potential prefusion

175 2 subtype that stabilizes the HA trimer in a prefusion-like state at and below fusogenic pH.

176 her, species-limited proteins, to form tight prefusion membrane attachments with their respective gam

177 f the F protein that lie at the heart of its prefusion metastability.

178 a homogeneous protein that retains critical prefusion neutralizing epitopes.

179 zing antibody (nAb) in complex with trimeric prefusion NiV-F reveals an epitope at the membrane-dista

180 microscopy, TraAB overexpression catalyzed a prefusion OM junction between cells.

181 s not affected by enhanced expression or the prefusion or postfusion conformation of RSV F.

182 Tgfb3 is strongly expressed in the prefusion palatal epithelium, and mice lacking Tgfb3 dis

183 ows very high similarity to the structure of prefusion parainfluenza virus 5 (PIV5) F, with the main

184 hat recognizes antigenic site II on both the prefusion (pre-F) and postfusion (post-F) conformations

185 structures of RSV fusion (F) glycoprotein in prefusion (pre-F) and postfusion (post-F) conformations,

186 lfide bond (DS) to increase stability in the prefusion (pre-F) conformation and to be efficiently pac

187 tein modified for increased stability in the prefusion (pre-F) conformation by previously described d

188 of RSV in either its postfusion (post-F) or prefusion (pre-F) conformation is a target for neutraliz

189 ncreased stability in the highly immunogenic prefusion (pre-F) conformation, with or without replacem

190 dates, and recent evidences suggest that the prefusion (pre-F) state is a superior target for neutral

191 undergoes a major structural shift from the prefusion (pre-F) to the postfusion (post-F) state at th

192 serum immunoglobulin G antibodies to the RSV prefusion (pre-F), postfusion (post-F), and G glycoprote

193 tant RSV F protein ectodomains stabilized in prefusion (pre-F/F) or postfusion (post-F/F) configurati

194 junction with the alpha-helical stalk of the prefusion protein.

195 This highly stable prefusion RSV F elicits neutralizing antibodies in cotto

196 Prefusion RSV F induced a larger quantity and higher qua

197 LP) vaccine candidates containing stabilized prefusion RSV F proteins provides significant levels of

198 eutralizing activity and bind selectively to prefusion RSV F with picomolar affinity.

199 Serum antibodies against the prefusion RSV fusion protein (pre-F) exhibit high neutra

200 side-in signalling, involving binding of the prefusion RSV-F glycoprotein with the insulin-like growt

201 associated with refolding of the metastable prefusion S glycoprotein to the postfusion conformation

202 e design of a construct corresponding to the prefusion SARS-CoV-2 S ectodomain trimer, covalently sta

203 Prefusion SARS-CoV-2 S is the main target of neutralizin

204 ine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adu

205 ate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein.

206 tes SNARE-complex assembly through promoting prefusion SNARE binary complex formation.

207 To overcome this obstacle, we identified prefusion-specific antibodies that were substantially mo

208 aved trimer, the uncleaved monomer binds the prefusion-specific monoclonal antibody D25 and human neu

209 fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV

210 3.2 angstroms confirmed that it retains the prefusion spike conformation.

211 High-yield production of a stabilized prefusion spike protein will accelerate the development

212 D-19) patients using a SARS-CoV-2 stabilized prefusion spike protein.

213 lizing CR3022 epitope is inaccessible in the prefusion spike, suggesting that CR3022 binding facilita

214 tures provide a foundation for understanding prefusion-spike mechanics governing endosomal entry; we

215 Prefusion stabilization conferred by a P22L-homologous m

216 ty of RSV F by packaging appeared to involve prefusion stabilization.

217 psulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the se

218 anzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (ChAd-SARS-CoV-2-S) i

219 cleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-

220 ntibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes.

221 We also engineered PIV5 to express a prefusion-stabilized F mutant.

222 e PIV5 backbone, replace native RSV F with a prefusion-stabilized RSV F mutant, or combine both RSV F

223 demonstrate that it enhances the opening of prefusion-stabilized RSV F trimers.

224 gy previously used for MERS-CoV to produce a prefusion-stabilized SARS-CoV-2 spike protein, S-2P.

225 zing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose.

226 100 mug of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no

227 assembling protein nanoparticle presenting a prefusion-stabilized variant of the F glycoprotein trime

228 s suggest that Munc18a primarily acts at the prefusion stage.

229 formers proposed to correspond to a tethered prefusion state and a postfusion state.

230 n a structured trimer thought to represent a prefusion state and an ensemble of unstructured monomers

231 s V3 and the coreceptor binding sites in the prefusion state and exposes them upon CD4 binding.

232 tosis by clamping trans-SNARE complexes in a prefusion state and promoting conformational changes to

233 "clamp" to keep the B loop in its metastable prefusion state at neutral pH, the "pH sensors" that are

234 F glycoprotein revealed D25 to lock F in its prefusion state by binding to a quaternary epitope at th

235 However, to reach the prefusion state collectively, starting from the experime

236 ulting SOSIP.v5.2 S306L/R308L trimers in the prefusion state in which V3 is sequestered.

237 ively than postfusion F, indicating that the prefusion state is more exposed to solvent and is more f

238 (Tys173 and Tys177) that in the CD4-unbound prefusion state mediate intramolecular interaction betwe

239 was used to activate F, indicating that the prefusion state of F can be triggered to initiate struct

240 results indicate that HN helps stabilize the prefusion state of F, and analysis of a stalk domain mut

241 tions in the arm may energetically favor the prefusion state of gB.

242 The structure shows a prefusion state of gp41, the interaction between the com

243 e final structure, little is known about the prefusion state of individual membrane-bound SNAREs and

244 The prefusion state of respiratory syncytial virus (RSV) fus

245 ic site O, a metastable site specific to the prefusion state of the RSV fusion (F) glycoprotein, as t

246 ng down an energy gradient from a metastable prefusion state to a highly stable postfusion state.

247 the first phase progresses from a metastable prefusion state to a prehairpin intermediate (PHI), whil

248 Conversion from the prefusion state to the postfusion state requires passage

249 interface form required to maintain F in its prefusion state until HN binds receptors.

250 bilize Betacoronavirus spike proteins in the prefusion state, improving their expression and increasi

251 thought to undergo structural changes from a prefusion state, in which S2-HR1 and S2-HR2 do not inter

252 The T/F100 structure might represent a prefusion state, intermediate between the closed and ope

253 e-embedded structure of synaptobrevin in its prefusion state, which determines its interaction with o

254 tein trimers that are trapped in the closed, prefusion state.

255 nsition state and a structured trimer in the prefusion state.

256 s inconsistent with that found in the native prefusion state.

257 clasp (gp41 W623, W628, W631) in the B41 Env prefusion state.

258 V entry, including interacting with gp120 in prefusion states and interacting with gp41 heptad repeat

259 priming factor Munc13 exclusively restricted prefusion states to point contacts, all of which efficie

260 ptotagmin-1, produced point and long-contact prefusion states.

261 eover, our observations indicate that the HA prefusion structure (and perhaps the metastable states o

262 t likely represents its postfusion form, its prefusion structure and the details of how it refolds to

263 articipate as a pH sensor by stabilizing the prefusion structure of GP64.

264 Because only the prefusion structure of the parainfluenza virus 5 (PIV5)

265 By comparison of SFTSV Gc with that of the prefusion structure of the related Rift Valley fever vir

266 Elucidation of the prefusion structure of the RSV F glycoprotein and its id

267 tions on the HR-B domain within the trimeric prefusion structure.

268 e relation of 'leaky' fusion to the observed prefusion structures is discussed.

269 e findings also suggest that the ensemble of prefusion structures presents many potential sites for t

270 efusion-like conformation and is a potential prefusion subunit vaccine candidate.

271 w characterization of structural elements in prefusion synaptobrevin and providing a framework for in

272 required to cause the refolding of gB from a prefusion to a postfusion conformation.

273 the refolding of glycoprotein B (gB) from a prefusion to a postfusion state.

274 tep in fusion is the conversion of gB from a prefusion to an active postfusion state by gH/gL, gB843

275 ly representing the refolding of gB from its prefusion to its postfusion conformation.

276 The transition from prefusion to postfusion conformation of the spike protei

277 into a target membrane and refolding from a prefusion to postfusion conformation to bring the viral

278 As F undergoes a dramatic refolding from its prefusion to postfusion conformation, the fusion peptide

279 vage and heat to transition from an apparent prefusion to postfusion conformation, transitioning thro

280 ide hydrolysis might not be required for the prefusion to postfusion conformational change.

281 eceptor-binding site and, subsequently, from prefusion to postfusion conformations to mediate fusion

282 lular components or for transitions from the prefusion to postfusion state.

283 ogen gB, which is thought to refold from the prefusion to the postfusion form in a series of large co

284 they change conformation from the unzippered prefusion to the zippered postfusion state in a membrane

285 hydrolysis, that converts the dimer from a "prefusion" to "postfusion" state.

286 he MPER epitopes, presumably in the putative prefusion transitional intermediate.

287 l organization of the MPER within the native prefusion trimer [(gp120/41)(3)] are elusive and even co

288 quaternary rearrangements compared with the prefusion trimer and rationalizing the free-energy lands

289 The prefusion trimer has three receptor-binding domains clam

290 is similar to other reported "closed" state prefusion trimer structures.

291 at redesigned Env closely mimics the native, prefusion trimer with a more stable gp41.

292 esistant to digestion and help stabilize the prefusion trimer, suggesting the glycan shield may funct

293 with CR3022 Fab leads to destruction of the prefusion trimer.

294 two adjacent GPC monomers and preserved the prefusion trimeric conformation.

295 BG505, yields a homogeneous and well ordered prefusion trimeric form, which maintains structural inte

296 ng cell entry, the cleaved Fs rearrange from prefusion trimers to postfusion trimers.

297 e structural and biochemical analysis of the prefusion variants suggests a function for p27, the exci

298 nucleoprotein and two engineered (linked and prefusion) versions of the glycoproteins (GP) of lineage

299 and demonstrate that targeted exocytosis of prefusion vesicles is a critical step prior to plasma me

300 olved in the proper targeting and coating of prefusion vesicles.