ライフサイエンスコーパス: interdomain

1 cs within the betaSBD play a central role in interdomain allosteric communication in the Hsp70 DnaK.

2 ilized substrate binding and interfered with interdomain allosteric coupling, marking ADP ribosylatio

3 ora B and Map205 in cytokinesis reveals that interdomain allosteric mechanisms can play important rol

4 FVIIa, underscoring a remarkable intra- and interdomain allosteric regulation of this trypsin-like p

5 We find that DNA binding triggers an interdomain allosteric regulation within the GR, leading

6 Understanding the mechanism of interdomain allostery is essential to rational design of

7 nd activity via coevolving residues, whereas interdomain allostery, critical to chaperoning, is robus

8 efolding activity in vitro without affecting interdomain allostery, interaction with co-chaperones Dn

9 oreover, mutations in this region compromise interdomain allostery.

10 ide, therefore, an example for destabilizing interdomain allostery.

11 tant in mediating short range and long range interdomain and intersubunit interactions that uniquely

12 2 is facilitated by the unusually wide D1-D2 interdomain angle in OSCAR.

13 in the Sylvatic genotype virus recognized by interdomain antibodies could be the major cause of the p

14 ate, suggesting that they perturb Phi29 DNAP interdomain architecture.

15 strate that perturbing a ctenophore-specific interdomain Arg-Glu salt bridge that is notably absent f

16 als ctenophore-specific features, such as an interdomain Arg-Glu salt bridge, present only in subunit

17 tially populated conformation that adopts an interdomain arrangement is suitable for building a funct

18 We observe that transient interdomain association, represented by an effective mol

19 Although mutations in the interdomain-B region affected ITK-SYK kinase activity, t

20 They also illustrate interdomain bending and flexibility around average confo

21 e chains of these residues participate in an interdomain bond, we prepared and examined the functiona

22 the Asp(203)-Arg(678) and Ser(186)-Glu(439) interdomain bonds are critical, because they tighten the

23 EGF2 and EGF3 constitute a rigid rod via an interdomain calcium ion binding site, the long linker be

24 ections, we defined MeV L position 615 as an interdomain candidate in addition to the previously repo

25 In addition, interdomain cleavage of Dredd is not required for Imd or

26 terminal domain, and site-4 is located in an interdomain cleft adjacent to the active site.

27 d II against each other to further close the interdomain cleft between subdomains IB and IIB.

28 tional density modeled as HEPES bound in the interdomain cleft close to the predicted catalytic Lys-1

29 rule, PBPs remain open until ligand-induced interdomain closure or are in equilibrium with a minor p

30 h may be achieved via linker-domain-mediated interdomain communication driven by ATP hydrolysis.

31 uding protein import, and requires effective interdomain communication for efficient partner-protein

32 ymes, like the PMT, provides new insights on interdomain communication in biosynthetic systems.

33 haracterization of these proteins shows that interdomain communication modulates the coordination sta

34 to the p97-ND1 interface, thereby modulating interdomain communication of p97 domains and its activit

35 dy, we engineered the transporter to dissect interdomain communication paths.

36 egions within the SBD of mtHsp70s regulating interdomain communication, thus highlighting its importa

37 eotide-binding domain (NBD), thus regulating interdomain communication.

38 implicating alpha3 and the linker in tuning interdomain communication.

39 teractions, bridges an essential pathway for interdomain communication.

40 se center remodel the nuclease center via an interdomain 'communication track'.

41 Investigation of long-range intra- and interdomain communications in the p53 tetramer-DNA compl

42 The new monomeric interdomain conformation in solution is significantly di

43 ollows a nucleation-propagation process, the interdomain conformational change might be a key step du

44 n with the membrane surface through a large, interdomain conformational change.

45 binding, participates in PIP(3)-induced Akt interdomain conformational changes for T308 phosphorylat

46 version of EsaR highlighted intradomain and interdomain conformational changes that occur in the pro

47 finity and thermostability by modulating the interdomain conformational dynamics of the antigen-bindi

48 for the capsid assembly remains: whether the interdomain conformer within a hexamer unit needs to be

49 ne, which indicates the importance of intact interdomain-connecting elements (i.e. hinge regions) for

50 ngs suggest that unique quaternary folds and interdomain connections in NRs could be exploited by sma

51 ted fatty-acid synthases also extends to the interdomain connections.

52 ture, films with high crystallinity and good interdomain connectivity are obtained.

53 y one order of magnitude for GBs with better interdomain connectivity.

54 have a unique architecture that features an interdomain connector (IDC) that joins the catalytic N-t

55 dent mobility, indicating that the bacterial interdomain connector lacks the rigidity that was found

56 rong evidence that TLS Pols bind PCNA at its interdomain connector loop (IDCL) via their PCNA-interac

57 Proteins make a connection within the interdomain connector loop of PCNA, and much of the regu

58 roteins for the interaction with PCNA at its interdomain connector loop.

59 - and beta-domains of HC form several unique interdomain contacts and have a higher shape complementa

60 n; however, no direct evidence for transient interdomain contacts has been observed in solution, and

61 due-specific information was obtained on the interdomain contacts in naturally-occurring K48-linked R

62 Alternatively, the interdomain contacts may be sufficient to drive the form

63 sotropic, comprising significantly populated interdomain contacts that appear to be electrostatic in

64 llectively bind to DNA, forming a network of interdomain contacts that links the DNA damage interface

65 ly, such as the requirement of disruption of interdomain contacts to trigger the alpha-to-beta transf

66 , and its channel assembly requires multiple interdomain contacts.

67 e activities are repressed by autoinhibitory interdomain contacts.

68 nced functionalities of full-length TrpRS on interdomain coupling energies between the two new module

69 Moreover, the A-site cAMP, by maintaining interdomain coupling, retards the unbinding of the B-sit

70 of potentially significant interresidue and interdomain couplings.

71 agonists and antagonists are anchored in the interdomain crevice of GBR1 by an overlapping set of res

72 e L164 and K165 side chains to stabilize the interdomain CRIB:PDZ interface and reposition a conserve

73 , as judged by resistance to proteolysis and interdomain cross-linking.

74 domain motion than GPA1 and instead displays interdomain displacement resembling that observed in a r

75 NADPH and calmodulin are shown to influence interdomain distance relationships as well as reaction c

76 Using pulsed EPR (PELDOR or DEER) to measure interdomain distances in solution, we have examined two

77 Interdomain distances measured by DEER have been employe

78 n resonance to determine the distribution of interdomain distances with high resolution.

79 e cysteine point mutants that engineer extra interdomain disulfide bridges rigidify the UGGT structur

80 cleaved by caspase-3 at a site in the C1-PH interdomain during apoptosis; the functional consequence

81 Most importantly, the segmental interdomain dynamics always increase the apparent substr

82 and efficient tool to probe and describe the interdomain dynamics and represents a general method tha

83 ed by a multidomain protein showing moderate interdomain dynamics in terms of translational and rotat

84 e use solution NMR spectroscopy to study the interdomain dynamics of CBD12, a 32 kDa construct that c

85 Notably, although a reduction in interdomain dynamics of UbcH5c~Ub is observed upon bindi

86 Therefore, the modulation of interdomain dynamics represents an important mechanism d

87 emonstrate that cpSRP43 exhibits significant interdomain dynamics that are reduced upon binding its S

88 hesis by NOS is primarily through control of interdomain electron transfer (IET) processes in NOS cat

89 ygenase domains that coordinate a multistep, interdomain electron transfer mechanism to oxidize l-arg

90 ction work also suggested Steap4 utilizes an interdomain flavin-binding site to shuttle electrons bet

91 tures, a 15-A cryo-EM reconstruction reveals interdomain flexibility of the TRXL domains.

92 molecular dynamics simulations to determine interdomain flexibility, Monte Carlo simulations of mult

93 f Ca(2+) to CBD1 significantly restricts the interdomain flexibility, stabilizing a more rigid elonga

94 l KaiA pseudoreceiver domains and/or reduced interdomain flexibility.

95 Interdomain flexing of the enzyme and a localized excurs

96 their catalytic rotation is associated with interdomain fluctuations and heterogeneity of conformati

97 y the magnitude and functional dependence of interdomain forces concurrently with the bending elastic

98 tes, the method enables the first test of an interdomain helix-swap hypothesis for ligand-binding coo

99 substantial fraction of this population was interdomain highly neutralizing flavivirus subgroup-cros

100 lar modeling suggests that alteration in the interdomain hinge angle of KIR2DL3*005 toward that found

101 flexibility for two regions of CK2alpha: the interdomain hinge region, and the glycine-rich loop (p-l

102 A series of conserved interdomain His residues is identified to be responsible

103 tion at nine sites, primarily located in the interdomain I-II linker, the region of Nav1.2 crucial fo

104 by nSMase2 and is governed by an allosteric interdomain interaction at the membrane interface.

105 These structures illustrate a unique interdomain interaction between the two ATPase domains i

106 Disruption of the repressive interdomain interaction by amino acid substitutions with

107 The observed interdomain interaction explains PMC's resistance to try

108 Interestingly, the interdomain interaction mutant displayed enhanced mRNA t

109 ction and formation of a predominantly polar interdomain interaction surface.

110 We used protein footprinting to map interdomain interaction surfaces of the sGC signaling do

111 tion between NS3 and NS5 as well as specific interdomain interaction within NS5 required for RNA repl

112 Integrins stabilized the RyR2 interdomain interaction, and this stabilization required

113 gral membrane proteins, such as topology and interdomain interaction, is key to a fundamental underst

114 rtant role for F130, in the stability of the interdomain interaction.

115 ted OCP has an open structure with decreased interdomain interaction.

116 However, it is unclear whether and how the interdomain interactions among the VSD, CTD, and PGD are

117 yrin deformation state, but it suggests that interdomain interactions are disrupted by the mutation.

118 hed compartments to establish new intra- and interdomain interactions associated with a B lineage-spe

119 positions 295, 141, and 363 are involved in interdomain interactions at the cytoplasmic side by gove

120 rminant of agonist efficacy, suggesting that interdomain interactions between the ABD and the ATD may

121 Interdomain interactions between the CH3 domains of anti

122 ct hormonal contact and/or by modulating the interdomain interactions between the hinge region (HinR)

123 Frustration from strong interdomain interactions can make misfolding a more seve

124 Changes at the interdomain interactions caused either AHR constitutive

125 Recent studies indicate that interdomain interactions critically influence UHRF1's ch

126 Under acidic pH, weakening of the interdomain interactions exposes individual domains, res

127 RET data, we were able to distinguish stable interdomain interactions from freely orienting domains.

128 case for HAI-1, where our results reveal how interdomain interactions have evolved to stimulate the i

129 ions, ligand-mediated residue couplings, and interdomain interactions in protein oligomers.

130 hich is strongly influenced by the nature of interdomain interactions in resting and active states, m

131 kinase correspond to two dynamic units, but interdomain interactions link the motion of the two doma

132 agenesis and functional assays, we show that interdomain interactions not only stabilize the fold of

133 cture that is stabilized by intersubunit and interdomain interactions of LRRNT and LRRCT in the trime

134 Interdomain interactions of spectrin are critical for ma

135 nhibition of VWF mediated by force-dependent interdomain interactions offers the molecular basis for

136 The effect of the interdomain interactions on the activation of motions in

137 introduce bulky residues into tight Gly-Gly interdomain interactions on the periplasmic side of LacY

138 ntial importance of Glu(521) and Glu(535) in interdomain interactions required for proper folding and

139 Together, our data reveal interdomain interactions responsible for communicating N

140 ain proteins that lack these specific strong interdomain interactions should fold reliably.

141 E2A or PU.1 were associated with intra- and interdomain interactions that are developmentally regula

142 ified oligonucleotides evolved by optimizing interdomain interactions that stabilize the catalyticall

143 ion of enzymatic activity, many DUBs utilize interdomain interactions to regulate catalysis.

144 G168D mutation was associated with weakened interdomain interactions under tensile force.

145 Upon light stimulation, interdomain interactions weaken to facilitate activation

146 ce motifs involved in ATP and RNA binding or interdomain interactions, as well as previously unidenti

147 athways, emanating from hydrophobic or polar interdomain interactions, differentially affecting lipid

148 decouples control over the domain shape and interdomain interactions, leading to a multiplicity of p

149 e scaffolding protein hRpn2/S1 abrogates its interdomain interactions, thus activating hRpn13 for ubi

150 e that the activity of Dhh1 is restricted by interdomain interactions, which can be regulated by cell

151 intradomain interactions but also increased interdomain interactions.

152 ion changes its conformation and/or mediates interdomain interactions.

153 otein concentration, and the strength of the interdomain interactions.

154 ivated FVIII (dis-FVIIIa), may contribute to interdomain interactions.

155 n but also through more global remodeling of interdomain interactions.

156 ensive heterodimerization interfaces and AHR interdomain interactions.

157 lly independent loops by insulators inhibits interdomain interactions.

158 affected by the dimerization interfaces and interdomain interactions.

159 amily but also how the two domains engage in interdomain interactions.

160 und that charges contain the information for interdomain interactions.

161 Thus, the structure and stability of this interdomain interface are crucial for the role of sigma(

162 nker is a well-structured participant in the interdomain interface in ATP-bound Hsp70s.

163 the active site and critical residues at the interdomain interface indicates that this mechanism is c

164 olding nucleus is disrupted by mutation, the interdomain interface is sufficiently stable to drive th

165 by acting as molecular wedges that restrict interdomain interface movement behind the selectivity fi

166 ion network connecting the active site to an interdomain interface responsible for nucleotide loading

167 coupled with the remarkable stability of the interdomain interface result in cooperative folding kine

168 istant conformation maintained by a critical interdomain interface within a negative regulatory regio

169 igma(N)-holoenzyme model reveals a conserved interdomain interface within sigma(N) that, when disrupt

170 model given the increased flexibility at the interdomain interface, and we can for the first time exp

171 reduction in the buried surface area at the interdomain interface.

172 binding pocket at one pole and an equatorial interdomain interface.

173 y conserved Ile and Phe residues at the RfaH interdomain interface.

174 form a rigid interaction through a conserved interdomain interface.

175 se inhibitor (APHI) that binds a site in the interdomain interface.

176 the domain structures and properties of the interdomain interfaces indicate that interconversion bet

177 Ca(2+), ATP, and caffeine were identified at interdomain interfaces of the C-terminal domain.

178 mutations establishes a correlation between interdomain interfaces of the enzyme and missense varian

179 binding of ankyrins, mutations altering the interdomain interfaces of ZZU impair the functions of an

180 isolated receiver domains of a RR that lacks interdomain interfaces, and they are not observed in his

181 Pervasive H-bonding is found at all interdomain interfaces, which may contribute to their ma

182 . kaustophilus HTA426 DnaK that contains the interdomain linker (acting as a pseudo-substrate), and t

183 by an unstructured approximately 80-residue interdomain linker (IDL).

184 rved and functionally crucial portion of the interdomain linker (residues ) and another that lacks th

185 Here we find that the interdomain linker also affects the single-base deletion

186 which the Ras-binding site is blocked by an interdomain linker and the membrane-interaction surface

187 This preferential binding implicates the interdomain linker as a dynamic allosteric switch.

188 tify a tetrapeptide motif (RXWV) in the TlyA interdomain linker as indispensable for co-substrate bin

189 The interdomain linker becomes statically disordered.

190 lammatory caspases cleave gasdermin-D in the interdomain linker but not GSDMB.

191 sults show that changing the sequence of the interdomain linker can profoundly affect the dimerizatio

192 ts an unexpected locus for the binding of an interdomain linker element in DnaI/DnaC-family proteins.

193 a-helical lid, and the conserved hydrophobic interdomain linker enable allosteric signal transmission

194 interface is created by the insertion of an interdomain linker from C6 into a hydrophobic groove cre

195 explore the conformational landscape of the interdomain linker in ADP-bound DnaK and supported our s

196 es, we have previously demonstrated that the interdomain linker is a major determinant of polymerase

197 The interdomain linker is a well-structured participant in t

198 fied by the Escherichia coli Hsp70 DnaK, the interdomain linker is flexible.

199 essfully capture the experimental effects of interdomain linker length and ligand binding on the exte

200 Finally, we investigate the relation between interdomain linker length and misfolding, and propose a

201 de-binding pocket and the conformation of an interdomain linker loop.

202 ore, we provide evidence that the disordered interdomain linker modulates the histone-binding affinit

203 Thus, the PH domain and the interdomain linker of Brag2 may be targets for selective

204 o consist of adjacent protomers engaging the interdomain linker of one molecule in the substrate bind

205 gma(K) depends on particular residues in the interdomain linker of SpoIVFB.

206 Mutations in the interdomain linker of the gene for the AraC regulatory p

207 o alters the packing of the highly conserved interdomain linker of the PER2 PAS core such that, altho

208 Our data provide an example of how interdomain linker plasticity can modulate the function

209 ) a four-Gly (FNIII9(4G)10) insertion in the interdomain linker region and used surface plasmon reson

210 We thus identify 10 residues in the interdomain linker region that change their conformation

211 construct, including residues comprising the interdomain linker region, revealed an expanded heterodi

212 on of histone binding by a histone-mimicking interdomain linker represents another example of regulat

213 We found that while the interdomain linker samples many conformations, it behave

214 Hsp70 interdomain linker sequences are highly conserved; moreo

215 ormational activation of AP-2 by the Fcho1/2 interdomain linker to promote AP-2 cargo engagement.

216 y disordered and may function as a flexible, interdomain linker, allowing a coupled interaction of th

217 teraction motif between W77 of S3, the S4-S5 interdomain linker, and the C-terminus, which is associa

218 d eIF4B/-3 binding site within the HEAT-1/-2 interdomain linker, harboring two phosphorylation sites

219 Thus, a small region of the interdomain linker, located more than 11 A away from the

220 and RRM1 as well as the participation of the interdomain linker, probably in realizing tandem domain

221 that the conformational fluctuations of the interdomain linker, which are largely responsible for th

222 rees ) at the end of the relatively immobile interdomain linker.

223 e PH domain and that activity depends on the interdomain linker.

224 site to the substrate-binding domain via the interdomain linker.

225 eyed from the nucleotide-binding site to the interdomain linker.

226 tone reader module, including its 20-residue interdomain linker.

227 d motions throughout both RRMs including the interdomain linker.

228 at binding by beta depends critically on the interdomain linker.

229 nding domain (SBD), which are tethered by an interdomain linker.

230 The role of interdomain linkers in modular polyketide synthases is p

231 Our findings further support the concept of interdomain linkers serving a dual role in substrate bin

232 es the interactions between protein domains, interdomain linkers, N- and C-terminal regions and prote

233 o by various non-structured regions, such as interdomain linkers, or terminal sequences.

234 an additional DNA-binding domain and longer interdomain linkers, the architecture of a canonical thr

235 riety of interdomain orientations due to two interdomain linkers.

236 M, there is high mobility in the two-residue interdomain linking sequence, with no preferred relative

237 and Arg-103, residues in the vicinity of the interdomain Lys-99-Asp-101 salt bridge, have little or n

238 omain proteins, yet it is not understood how interdomain misfolding is avoided.

239 rotein is further slowed by the formation of interdomain misfolds, suggesting that with growing chain

240 , in magnetically aligned media, to evaluate interdomain motion is established but only for two-domai

241 ding of general relevance is that changes in interdomain motion on trans-binding have a crucial role

242 The interdomain motion turns out to be limited.

243 n, and little is known about how large-scale interdomain motions contribute to biological function.

244 Challenges encountered in deciphering interdomain motions for this ternary complex are discuss

245 NMR has revealed substantial interdomain motions in CaM-4Ca(2+), enabled by a flexibl

246 sis to determine the role of intradomain and interdomain motions in conferring distinct activation ra

247 Here, we characterize the interdomain motions in the calcium-bound state of calmod

248 ulations allowed for the characterization of interdomain motions of a compact state of PGK.

249 hich are largely responsible for the overall interdomain motions of CaM, can be well described by exp

250 lations have captured functionally important interdomain motions of NS3 helicase and reproduced singl

251 Furthermore, in MD, interdomain motions on a timescale of approximately 10 n

252 led because mutations were incompatible with interdomain motions required for catalysis.

253 These large-scale interdomain motions shed light on the structural transit

254 a high flexibility of Scl2.3 with remarkable interdomain motions that are likely instrumental to the

255 laxation data have been used to characterize interdomain motions.

256 nder three different conditions, to estimate interdomain motions.

257 sidue for FA locking and also for triggering interdomain movements in EF-G essential for its function

258 The interdomain opening is coupled to receptor binding via t

259 lly harbor a buried ligand-binding pocket at interdomain or intersubunit clefts, facilitating proper

260 d consistently located within or near to the interdomain or solvent-exposed regions in the antibody s

261 The relationship between interdomain order disparity and the stability of phase s

262 that this binding mode likely influences the interdomain orientation.

263 l fold, these domains exhibited a variety of interdomain orientations due to two interdomain linkers.

264 Ca(v)1.2 (IQ), which adopts three different interdomain orientations in the crystal.

265 rangements comprise significantly non-linear interdomain orientations.

266 Simultaneous with these interdomain perturbations, DeltaF508 resulted in suppres

267 ordered, cholesterol-poor/PSM-rich/DOPC-rich interdomain phase.

268 fate and p-cresol sulfate dock on a putative interdomain pocket of the extracellular EGF receptor.

269 1*005 correlated with an altered KIR3DL1*005 interdomain positioning and increased mobility within it

270 dergoes one of the largest substrate-induced interdomain rearrangements documented to date.

271 osomal translocation is accompanied by large interdomain rearrangements of elongation factor G (EF-G)

272 d to brain endothelium and the cysteine-rich interdomain region 1 inhibited binding of P. falciparum-

273 The NMR resonances of this interdomain region exhibited chemical shift changes upon

274 68D replacement along the AD facing the CfaE interdomain region was previously shown to decrease the

275 within the micrometer-scale domains and the interdomain region.

276 ree compositionally distinct phases: (1) the interdomain region; (2) micrometer-scale domains (d > 3

277 s partitioned by two flexible linkers termed interdomain regions (IDRs).

278 ar ectodomains made from CIDR (cysteine-rich interdomain regions) and DBL (Duffy-binding-like) domain

279 n the DBL2X domain and parts of the flanking interdomain regions.

280 Aiming to uncover interdomain regulatory mechanisms in SHIP2, we determine

281 hosphorylation of Asp(60) of AccR alleviates interdomain repression mediated by the N-terminal domain

282 MrkH structures reveals a large 138 degrees interdomain rotation that is induced by binding an inter

283 he separation between domains increased, and interdomain rotations became more frequent.

284 ecular dynamics simulations suggest that the interdomain salt bridge acts as a steric barrier regulat

285 ich appears to be stabilized by a network of interdomain salt bridges and hydrogen bonds, and reveals

286 dynamics simulations identified three novel interdomain salt bridges in the lymphomagenic virus HR1

287 s and are closed at the matrix side by three interdomain salt-bridge interactions, one of which is br

288 hypothesize conformational plasticity in an interdomain segment of FliG that allows some subunits to

289 in an extended conformation with significant interdomain separation, but clamps down upon target pept

290 s, so as to establish the dynamical basis of interdomain signal transduction in Hsp70s.

291 A primary reason why study of interdomain signaling is challenging in oligomeric prote

292 ted by fatty acid binding to a high-affinity interdomain site that disrupts at least one Zn site.

293 We characterize here interdomain site-to-site communication by which a common

294 ndividual CBD1 and CBD2 are available, their interdomain structure and dynamics and the atomic level

295 Recently, a Ca(2+)-driven interdomain switch has been described, albeit how it cou

296 The latter structural elements make interdomain tertiary contacts (L5/P3) that span a region

297 ed to approximately 40 degrees variations of interdomain torsional angle, are revealed.

298 nd C-terminal domains, including an extended interdomain tunnel associated with substrate channeling.

299 which is dependent on temperature-sensitive interdomain unfolding and cis-trans prolyl isomerization

300 odine receptor 2 [RyR2]) in heart failure is interdomain unzipping that can enhance aberrant channel