ライフサイエンスコーパス: prefusion

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

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

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

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

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

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

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

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

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

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

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

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

13 in two structurally distinct conformations, prefusion and postfusion.

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

15 depend on temperature-dependent elements on prefusion antigens, whereas cluster I and cluster II epi

16 figuration designed to approximate activated prefusion assemblies from neuronal and viral fusion, pro

17 "Prefusion" assembly intermediate complexes can also form

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

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

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

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

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

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

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

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

26 iate step in the process, the formation of a prefusion complex consisting of "paired vesicles." These

27 This prefusion complex resolves into dense membrane plaques b

28 that is essential for progression beyond the prefusion complex stage.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

55 hydrophobic fusion peptide is hidden in the prefusion conformation, becomes exposed once the fusion

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

57 f the parainfluenza virus 5 F protein in its prefusion conformation, stabilized by the addition of a

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

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

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

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

62 ary to establish and maintain the metastable prefusion conformation.

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

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

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

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

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

68 e there is no structural information for the prefusion conformations of SARS-CoV HR1 and HR2.

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

70 How the prefusion conformer transitions to the postfusion confor

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

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

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

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

75 of domain II is different from that in other prefusion E structures, however, and resembles the confo

76 three-dimensional structural studies of the prefusion e-gp41 and serve to guide future attempts at p

77 strongly suggest that this mini-Env adopts a prefusion e-gp41 configuration that is strikingly distin

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

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

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

81 molecular structure of a soluble form of the prefusion F (PIV5 F-GCNt) with the biological function o

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

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

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

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

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

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

88 Although prefusion F induces higher levels of neutralizing antibo

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

107 These prefusion F-specific VHHs represent promising antiviral

108 head domain of the attachment protein above prefusion F.

109 dies recognize epitopes found exclusively in prefusion F.

110 with more pathology after challenge than was prefusion F.

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

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

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

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

115 structure, which is the first example of the prefusion form of coronavirus envelope, supports the cur

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

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

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

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

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

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

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

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

124 rimer may not be required for folding of the prefusion form of the protein.

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

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

127 The prefusion form of these envelope glycoproteins thus repr

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

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

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

131 ght to undergo conformational changes from a prefusion form to a subsequent post-fusion form that ena

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

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

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

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

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

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

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

139 veals striking differences from the dimeric, prefusion form.

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

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

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

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

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

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

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

147 bind to a transiently exposed surface on the prefusion intermediate state of gp41 and disrupt subsequ

148 At the prefusion intermediate state, CP-1 could bind to the HR1

149 branes to generate a vesicle-plasma membrane prefusion intermediate that is poised for conversion to

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

151 e postfusion form without first adopting the prefusion intermediate.

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

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

154 2 subtype that stabilizes the HA trimer in a prefusion-like state at and below fusogenic pH.

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

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

157 Interestingly, this prefusion mini-Env, lacking the fragment containing the

158 c expression in presumptive muscle founders, prefusion myoblasts, and differentiated muscle fibers.

159 myoferlin is highly expressed in elongated "prefusion" myoblasts and is decreased in mature myotubes

160 y inadequate ribosomal RNA production in the prefusion neural folds during the early stages of embryo

161 e increase in the levels of apoptosis in the prefusion neural folds, which are the site of the highes

162 a homogeneous protein that retains critical prefusion neutralizing epitopes.

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

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

165 nes M-CSF- and adhesion-induced signaling in prefusion osteoclasts (pOCs) derived from Src-deficient

166 grin-mediated cytoskeletal reorganization in prefusion osteoclasts in the absence of c-Src, possibly

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

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

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

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

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

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

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

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

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

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

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

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

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

180 Prefusion RSV F induced a larger quantity and higher qua

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

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

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

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

185 Prefusion stabilization conferred by a P22L-homologous m

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

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

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

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

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

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

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

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

194 important in the folding of the metastable, prefusion state and the subsequent triggering of membran

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

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

197 2 cells can be poised at a late postdocking, prefusion state by MgATP-dependent priming processes cat

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

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

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

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

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

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

204 Until now, the prefusion state of gp41 ectodomain (e-gp41) has eluded m

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

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

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

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

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

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

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

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

213 120 core, in a conformation representing its prefusion state, before interaction with CD4.

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

215 ion plays a critical role in stabilizing the prefusion state, likely through interactions with heptad

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

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

218 gions are sufficient to maintain e-gp41 in a prefusion state.

219 cs that establish and maintain a metastable, prefusion state.

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

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

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

223 pecifically required for an insulin-mediated prefusion step involving the recruitment and/or docking

224 inhibited neurotransmitter release at a late prefusion step of synaptic vesicle exocytosis.

225 indicating that NSF acts at an ATP-dependent prefusion step rather than at fusion itself.

226 to independently regulate both fusion and a prefusion step(s).

227 by acting at a rate-limiting, Ca2+-dependent prefusion step.

228 Essential prefusion steps in dense-core vesicle exocytosis involve

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

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

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

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

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

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

235 ed structure being different from the native prefusion structure.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

261 Finally, palatal shelves from prefusion wild-type mouse embryos cultured in the presen