ライフサイエンスコーパス: autoinhibition

1 ed by the adjacent repeat Ig20, resulting in autoinhibition.

2 are caused by the release of talin head-rod autoinhibition.

3 ro DNA binding activity of ETV4 by relieving autoinhibition.

4 gical responses to dopamine D2-receptor (D2) autoinhibition.

5 rming the functional importance of E3-ligase autoinhibition.

6 endently of the well-known N-terminal domain autoinhibition.

7 ut not to recruitment kinetics or release of autoinhibition.

8 the CSH domain, which could function in ACLY autoinhibition.

9 talin molecule, thus achieving the state of autoinhibition.

10 at the C terminus and its deletion relieves autoinhibition.

11 nding to CBD sterically interferes with this autoinhibition.

12 asmic domain of STIM1 (STIM1-CT) that entail autoinhibition.

13 gulatory element in the RFTS domain-mediated autoinhibition.

14 f the other subunit, possibly accounting for autoinhibition.

15 The behavior of ETS1 is further regulated by autoinhibition.

16 rmation by the Arp2/3 complex, indicative of autoinhibition.

17 nating pivotal residues that ensure receptor autoinhibition.

18 gering a conformational switch relieving its autoinhibition.

19 ts function has been hypothesized to involve autoinhibition.

20 peats within the SRR dramatically reinforces autoinhibition.

21 T50I, V152G, and D153V Ras mutants evade SOS autoinhibition.

22 ies to distal ADAMTS13 domains relieves this autoinhibition.

23 t regions of these phospholipases to release autoinhibition.

24 The activity of PMCAs is controlled by autoinhibition.

25 ts catalytic Dbl homology (DH) domain confer autoinhibition.

26 at functions with the CARD to promote CARD11 autoinhibition.

27 gments to elucidate the mechanism of this FV autoinhibition.

28 toxins to protect rhs(+)/wapA(+) cells from autoinhibition.

29 ts binding activity with p53TAD is masked by autoinhibition.

30 etween PRR and WH2 and is subject to similar autoinhibition.

31 to PIP2, and PIP2-induced release of moesin autoinhibition.

32 ht of the fact that Capu can be regulated by autoinhibition.

33 membrane, unleashing the kinase domain from autoinhibition.

34 onal change that results in its release from autoinhibition.

35 ane binding of Ste5 triggers release of this autoinhibition.

36 e CdiA-CT and blocks its activity to prevent autoinhibition.

37 lex, suggesting a role for the N-terminus in autoinhibition.

38 of interacting proteins, and modulate enzyme autoinhibition.

39 entral to the maintenance and release of the autoinhibition.

40 ty protein (CdiI) protects CDI(+) cells from autoinhibition.

41 inal region of Sos, in the regulation of Sos autoinhibition.

42 ng of membrane recruitment to the release of autoinhibition.

43 drome protein (WASP) that result in aberrant autoinhibition.

44 -170 conformational changes resulting in its autoinhibition.

45 g, inducing opening of the loader to release autoinhibition.

46 plays an important role in regulating dynein autoinhibition.

47 spase-recruitment module besides its role in autoinhibition.

48 bs) to distal ADAMTS13 domains relieves this autoinhibition.

49 rstoichiometric quantities owing to putative autoinhibition.

50 ctor by a mechanism that we call facilitated autoinhibition.

51 reby suggesting the molecular basis of TrioC autoinhibition.

52 rgely mediated by relief of WW domain linker autoinhibition.

53 e Ig20 structure that supposedly weakens the autoinhibition.

54 cognition helix of the ETS domain to mediate autoinhibition.

55 minal and catalytic domains mediates ARTEMIS autoinhibition.

56 regulatory domains in maintaining catalytic autoinhibition.

57 d kinesin heavy chain (KHC) that relieve KHC autoinhibition, activating motor function in single mole

58 clashes that release the kinase domain from autoinhibition, allowing it to undergo a large conformat

59 models propose Dsn1 phosphorylation relieves autoinhibition, allowing Mis12C binding to inner kinetoc

60 Transformation-coupled autoinhibition allows RfaH to achieve high specificity a

61 and or antibodies to overcome the pre-ligand autoinhibition allows TMH clustering and thus signaling.

62 tination can also be influenced by WW linker autoinhibition, although to differing extents.

63 demonstrate distinct and common features of autoinhibition among gasdermin family members utilizing

64 tributes to our understanding of gasdermin D autoinhibition and activation and will inform the future

65 NRR, these studies show that key features of autoinhibition and activation are shared among different

66 nism, suggesting that a diverse mechanism of autoinhibition and activation might be adopted by member

67 lucidate the structural and dynamic bases of autoinhibition and activation of the kinase domain of Ca

68 tween these domains that we propose mediates autoinhibition and activation upon injury.

69 s A plexins, revealing its dual role in both autoinhibition and activation.

70 ich together reveal molecular details of its autoinhibition and activation.

71 s from folding defects and the disruption of autoinhibition and activation.

72 sphorylated in its SH3 domain which disrupts autoinhibition and allows GukH recruitment by the GK dom

73 ontaining molecule that adopts CCD-dependent autoinhibition and alternative splicing-dependent actin

74 thogen C. difficile that is not regulated by autoinhibition and challenge the current dogma that all

75 ctural model of Ezrin-Radixin-Moesin protein autoinhibition and cycling between closed/resting and op

76 his also results in progressively reinforced autoinhibition and decreased DNA-binding affinity.

77 e CN-calmodulin complex, relieving enzymatic autoinhibition and enabling CN substrate recognition.

78 at the DdMyo7 lever arm plays a role in both autoinhibition and function while the proximal tail regi

79 ss to the pyrin B-box domain responsible for autoinhibition and hence may be constitutively active.

80 ta explain how Ct deletions in XLP alleviate autoinhibition and increase enzyme activity.

81 and PYD-PYD interactions important for AIM2 autoinhibition and inflammasome assembly.

82 provide insights into the mechanisms of AIM2 autoinhibition and inflammasome assembly.

83 ed insight on the role of IR dynamics in HCN autoinhibition and its release by cAMP.

84 domains reveals a direct correlation between autoinhibition and membrane translocation following PKC

85 proximately 80-residue span is important for autoinhibition and needs to be released from both kinase

86 n constitutively active proteins, freed from autoinhibition and no longer influenced by nitrate.

87 show that (1) the DAD has dual functions in autoinhibition and nucleation; (2) the FH1, FH2, and DAD

88 nt in the PH domain that appears to regulate autoinhibition and PDK1-catalyzed phosphorylation of Thr

89 e demonstrate that Sec7 is regulated by both autoinhibition and positive feedback.

90 rotein lattice via MIT domains also relieves autoinhibition and primes the AAA ATPase cassettes for s

91 T8-CUB domains to the VWF D4 domain relieves autoinhibition and promotes cleavage of the nearby VWF A

92 ed C-terminal extension of Dcp2, alleviating autoinhibition and promoting substrate binding.

93 ents in the endosome, causing alleviation of autoinhibition and receptor activation.

94 Here we report the mechanisms of autoinhibition and release that control the activity of

95 ding step that maintains the fidelity of PKC autoinhibition and reveals a prominent loss-of-function

96 intramolecular regulatory mechanisms such as autoinhibition and subsequent activation.

97 osphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the eight Sr

98 critical roles of SFK SH2 domains in kinase autoinhibition and T-cell receptor signaling, monobodies

99 e C terminus of the protein counteracts this autoinhibition and that both the N- and C-terminal regio

100 ogenic regulator, appears to be regulated by autoinhibition and that the possible hinge motion of the

101 ibution of each phosphorylation site to PTEN autoinhibition and the structural basis for the conforma

102 lated in cis, thereby autonomously relieving autoinhibition and thus allowing subsequent adenylylatio

103 3 domain-containing Cb variants by relieving autoinhibition and thus define an alternative GTPase-dri

104 on of the PTEN C-tail phospho-cluster showed autoinhibition, and conformational closure was influence

105 between inhibitory helix stability and ETV6 autoinhibition, and demonstrate that helix unfolding doe

106 s to local unfolding of the HD that relieves autoinhibition, and has important implications for the d

107 structural requirements for cargo transport, autoinhibition, and regulatory mechanisms in myosin V mo

108 interacts with talin, relieves its state of autoinhibition, and triggers integrin activation.

109 Autoinhibition apparently modulates ETS1 DNA binding aff

110 esidues of the ankyrin-B linker required for autoinhibition are encoded by a small exon that is highl

111 sa; and why (iii) mutations that relieve the autoinhibition are likely to be drivers-even if they are

112 emonstrated that DAD roles in nucleation and autoinhibition are separable.

113 indings point to KA1-mediated intramolecular autoinhibition as a key regulatory mechanism of human Ch

114 CTD binding apparently releases autoinhibition because mutation of Tyr97 to phenylalanin

115 inhibitors can straightforwardly relieve the autoinhibition but not vice versa; and why (iii) mutatio

116 in-1 and kinesin-3 families are regulated by autoinhibition, but little is known about the mechanisms

117 dforward mechanism that involves reversal of autoinhibition by a tyrosine kinase associated with inte

118 tent oncogenic CARD11 mutations must perturb autoinhibition by at least three repressive elements.

119 Here, we show that Arf6-GTP relieves autoinhibition by binding to an allosteric site that inc

120 overed a dimeric state of UBE2S that confers autoinhibition by blocking a catalytically critical ubiq

121 in homology domain but also facilitates ASK1 autoinhibition by bringing the thioredoxin-binding and k

122 lucidated the physicochemical basis for ETS1 autoinhibition by characterizing the interaction of its

123 , we elucidate the structural basis for this autoinhibition by determining the structure of a region

124 ) and that c-di-GMP releases STING from this autoinhibition by displacing the CTT.

125 nucleotide exchange by the Sec7 domain, and autoinhibition by elements proximal to the PH domain are

126 nts showed that RNA polymerase relieves this autoinhibition by interacting with the C-tail and engagi

127 een postulated that ARTEMIS is regulated via autoinhibition by its C terminus.

128 chanisms, the most important of which is the autoinhibition by its C-terminal tail.

129 monomeric TbAdoMetDC is inactive because of autoinhibition by its N-terminal sequence.

130 the transition state barrier (ka), releasing autoinhibition by nSH2.

131 his interaction also contributes directly to autoinhibition by precluding a highly conserved dipole-e

132 eighboring cells and protect themselves from autoinhibition by producing specific immunity proteins.

133 The 14-3-3 cradle maintains autoinhibition by sequestering the membrane-binding cyst

134 inus of the h4xb PMCA causes partial loss of autoinhibition by specifically increasing the Vmax.

135 ealed multiple modes of binding that lead to autoinhibition by synergistically blocking the DNA-bindi

136 netrates the kinase active site, reinforcing autoinhibition by the activation loop.

137 observations were made with TFB2M, although autoinhibition by the C-tail of TFB2M was not as complet

138 LI induce CARD11 hyperactivity by disrupting autoinhibition by the CARD11 ID.

139 nstream adapter ASC only upon release of the autoinhibition by the dsDNA ligand.

140 and DNA binding domains (DBD) of AR, and its autoinhibition by the N terminus of AR.

141 large conformational rearrangement, whereby autoinhibition can be relieved by competitive sequestrat

142 ear magnetic resonance spectroscopy that the autoinhibition can be relieved by integrin or integrin r

143 II/III mGluRs maintain an activity-dependent autoinhibition, capable of significantly reducing TRPV1-

144 lanoblast migration in vivo Specifically, an autoinhibition-defective talin mutant strengthens and st

145 A full-length, autoinhibition-deficient mutant (T12) increases adhesion

146 Therefore, autoinhibition delays the multiple consequences of activ

147 We find that Akt autoinhibition depends on the length/flexibility of the

148 nisms, including the permanent removal of an autoinhibition documented here.

149 -1A receptors (5-HT(1A)), separated for 5-HT autoinhibition (dorsal raphe nucleus) and local inhibiti

150 addition, mutants of PLC-beta3 with crippled autoinhibition dramatically accelerated the hydrolysis o

151 The autoinhibition effect of the pilin domain is removed by

152 Autoinhibition enables spatial and temporal regulation o

153 Binding of eIF4E counteracts this autoinhibition, enabling eIF4G to stimulate eIF4A helica

154 osphorylation by Ipl1/Aurora B relieves this autoinhibition, enabling MIND to join an assembling kine

155 Collectively, disruption of normal Zap70 autoinhibition engaged negative feedback mechanisms by w

156 Mutations that impair the linker autoinhibition enhance the affinity for weak Py-tracts r

157 h domain liberates the catalytic domain from autoinhibition, enhancing enzymatic activity toward a pe

158 to probe the effect of the mutations on the autoinhibition equilibrium of the CBD, we find that when

159 To probe further the thermodynamic basis of autoinhibition, ETV6 variants were generated with amino

160 In the presence of AdoMet, the autoinhibition exerted by the regulatory region is elimi

161 Mice with defective talin autoinhibition exhibit delays in melanoblast migration a

162 antly related PU.1 in vitro, indicating that autoinhibition exploits features of the ETS domain that

163 lecular switch that promotes release of BicD autoinhibition following cargo binding to the neighborin

164 ween allosteric driver mutations, release of autoinhibition, free energy landscapes, and targeted pha

165 imulated by the reversible relief of amidase autoinhibition governed by conserved subcomplexes within

166 lar FRET analysis shows Galpha13 can relieve autoinhibition in a cellular milieu.

167 -specific up-regulation of GABA(B)R-mediated autoinhibition in CCK(+) BCs promotes aberrant high freq

168 ramolecular association, resulting in poorer autoinhibition in phosphorylated parkin.

169 n of ACAP1 relieves a localized mechanism of autoinhibition in regulating cargo binding.

170 aled a distinctive mechanism for DNA-binding autoinhibition in the ETV1/4/5 subfamily involving a net

171 t this may have significance for maintaining autoinhibition in the non-phosphorylated basal state of

172 uction enables efficient, stepwise relief of autoinhibition: initial phosphorylation events disrupt t

173 is fragility, we demonstrate how to engineer autoinhibition into the kinase so that phosphotransfer i

174 In contrast to existing models, we find that autoinhibition involves a conformeric equilibrium of the

175 Autoinhibition involves the intramolecular interaction b

176 Thus, autoinhibition is a conserved feature of Plks.

177 This work supports the model that autoinhibition is a general mechanism for regulation of

178 ein, we also have uncovered that IpaH family autoinhibition is achieved by a short-circuiting mechani

179 ial for melanoblast migration and that talin autoinhibition is an important mechanism for fine-tuning

180 However, it has also been hypothesized that autoinhibition is assisted by entropic losses caused by

181 In contrast to Ets-1, in which the autoinhibition is caused by a combination of allosteric

182 and cell biological techniques to show that autoinhibition is conserved in budding yeast, and plays

183 insufficient to define how release of basal autoinhibition is coupled to phosphorylation-dependent e

184 This autoinhibition is driven by favorable interactions betwe

185 Relief of SMURF2 autoinhibition is induced by TGFbeta and is mediated by

186 echanism whereby the allosteric basis of ERG autoinhibition is mediated predominantly by the regulati

187 This autoinhibition is neutralized when Cdk1 phosphorylates t

188 a putative coiled-coil domain (CCD) and the autoinhibition is overcome by alternative splicing regul

189 In response to calcium signaling, autoinhibition is reinforced by calmodulin-dependent kin

190 sponse to Ras-activating cell signaling, SOS autoinhibition is released and is followed by accelerati

191 MORC3 autoinhibition is released by disrupting the intramolecu

192 In the case of Plk4, autoinhibition is relieved after homodimerization and is

193 Autoinhibition is relieved by the binding of Ca(2+)-calm

194 o similar, yet distinct, mechanisms by which autoinhibition is relieved in the course of canonical CA

195 This autoinhibition is relieved upon introduction of the W24A

196 an inactive state without activators and how autoinhibition is relieved.

197 ibited by BMP signaling itself, and that BMP autoinhibition is required for resetting ISC pool size t

198 Autoinhibition is required for the in vivo biological ac

199 inactive DegS, but it is not known how this autoinhibition is reversed during activation.

200 ensively investigated, the mechanism of EPAC autoinhibition is still not fully understood.

201 r data show that force-independent relief of autoinhibition is sufficient to mediate their tight inte

202 the pseudosubstrate domain is necessary for autoinhibition it is not sufficient.

203 nal migration through attenuation of kinesin autoinhibition leading to aberrant KIF21B motility activ

204 ymphoma (DLBCL) and that disrupt ID-mediated autoinhibition, leading to constitutive NF-kappaB activi

205 that KIF1Bbeta binding releases calcineurin autoinhibition, leading to dephosphorylation of the DRP1

206 Together with evidence for ECT2 autoinhibition limiting interaction with CYK4 in the cyt

207 y provides a framework for understanding the autoinhibition, lipid binding, and oligomerization of GS

208 Autoinhibition maintains these catalytic ligases in an i

209 inhibition, we define a new function of ETS1 autoinhibition: maintenance of a monomeric state in the

210 ain, which are all important domains for the autoinhibition mechanism and downstream signal pathway r

211 This autoinhibition mechanism could extend to some other kine

212 Many formin proteins are regulated by an autoinhibition mechanism involving intramolecular bindin

213 This autoinhibition mechanism is believed to regulate the rol

214 sts that SmyD1 appears to be regulated by an autoinhibition mechanism, and that unusually spacious ta

215 However, the autoinhibition mechanism, as well as the physicochemical

216 ression of PTPN22 is partly attributed to an autoinhibition mechanism, in which PTPN22 suppresses its

217 cylation could potentially be involved in an autoinhibition mechanism.

218 To obtain evidence for the autoinhibition model, we performed co-immunoprecipitatio

219 By disrupting WASP autoinhibition, mycolactone leads to uncontrolled activa

220 constructs, we established that release from autoinhibition occurs in two distinct steps: rapid autop

221 stablish a dual role for the macro domain in autoinhibition of ALC1 ATPase activity and coupling to n

222 ion, uncovered how cytochrome c releases the autoinhibition of Apaf-1 through specific interactions w

223 ation between the N and C termini results in autoinhibition of CLIP-170, thus altering its binding to

224 flanking the ERG Ets domain responsible for autoinhibition of DNA binding and solved crystal structu

225 ngthens the AD2-DBD interaction and leads to autoinhibition of DNA binding even in the absence of Thr

226 We report the molecular basis of DNA-binding autoinhibition of ETS transcription factors ETV1, ETV4 a

227 of the hydrophobic helices and sheets to the autoinhibition of IRF-7 in the absence of viral signal.

228 philin and explains a possible mechanism for autoinhibition of its function through an intramolecular

229 plex renders dynein-2 monomeric and relieves autoinhibition of its motility.

230 ing that ensconsin plays a role in relieving autoinhibition of kinesin-1.

231 imics the interaction with p53, resulting in autoinhibition of MDMX.

232 escribed Ca(2+)-dependent C2 domain-mediated autoinhibition of Nedd4-2 is not observed under our repo

233 CaM conformation targets nSH2 to release its autoinhibition of p110 catalytic sites.

234 of DIR gives insight into the regulation of autoinhibition of pDA VTA neurons, and the resulting lon

235 of p38gamma to PTPN4 abolishes the catalytic autoinhibition of PTPN4 and thus activates the phosphata

236 duction of Ni(II) to Ni(0) and counteracting autoinhibition of reduction at Zn(0) by Zn(II) salts.

237 near cholinergic release sites, resulting in autoinhibition of release.

238 Here we report the structural basis for the autoinhibition of RIAM by an intramolecular interaction

239 s a template for SNARE complex assembly, and autoinhibition of synaptobrevin binding contributes to e

240 The leucine latch motif mediates the autoinhibition of the ATPase and chromatin-remodeling ac

241 kers in NEDD4-1 and WWP2, in contributing to autoinhibition of the catalytic HECT domains by intramol

242 nd active Arf GTPases that, in turn, relieve autoinhibition of the catalytic Sec7 domain through an u

243 2+)-bound calmodulin (Ca(2+)/CaM) to relieve autoinhibition of the catalytic subunit (CNA) by its C t

244 no)benzoic acid (PT-1), which attenuates the autoinhibition of the enzyme AMPK, for the design and sy

245 Such linker-mediated autoinhibition of the HECT domain can be relieved by lin

246 Phosphorylation increases autoinhibition of the intact complex.

247 CFEOM1-associated mutations relieve autoinhibition of the KIF21A motor, and this results in

248 at this compact docking is important for the autoinhibition of the kinase domains and for setting the

249 nd biochemical reconstitution, we found that autoinhibition of the Mis12C by Dsn1 impedes its phospho

250 partners, allowing common properties such as autoinhibition of the motor and microtubule binding to a

251 d trafficking domains relieves linker region autoinhibition of the VSE to produce maximal activation

252 This implies autoinhibition of the VWF for the binding of platelets m

253 n enterocytes, which provided a mechanism of autoinhibition of TLR4 signaling in enterocytes.

254 Our studies suggest that autoinhibition of UvrA binding in TRCF may be relieved o

255 Overall, autoinhibition of VWF mediated by force-dependent interd

256 GTPases play an important role in relieving autoinhibition, other factors likely contribute.

257 on of Sec7, the trans-Golgi Arf-GEF, through autoinhibition, positive feedback, dimerization, and int

258 Selective disruption of Munc13 autoinhibition profoundly impacts nervous system functio

259 PlexinD1 binding to GIPC1 releases the autoinhibition, promoting its interaction with myosin VI

260 he lysosomal membrane but also relieves SKIP autoinhibition, promoting kinesin-1-driven, anterograde

261 itution is not correlated with the change in autoinhibition properties.

262 Autoinhibition provides a novel structural platform that

263 an motor or stalk mutations attenuate Kif21a autoinhibition, providing in vivo evidence for mammalian

264 regulation of CaMKII function, manifested as autoinhibition (pT305 phosphorylation) followed by autoa

265 Autoinhibition release involves structural rearrangement

266 This autoinhibition release mechanism allows cargo-activated

267 This autoinhibition-relief mechanism is conserved with that o

268 CN channel showing that the well-established autoinhibition-relief model is insufficient.

269 we demonstrate that phosphorylation-enhanced autoinhibition requires the presence of phenylalanine or

270 n the pseudosubstrate of PKCbeta that impair autoinhibition result in dephosphorylated and unstable e

271 ver pathogenic Parkin mutations disrupt this autoinhibition, resulting in a constitutively active mol

272 cs, we also demonstrated that disrupting the autoinhibition results in a vastly activated enzyme comp

273 m its role in the CXXC domain-mediated DNMT1 autoinhibition, serves as an important regulatory elemen

274 ral determinants for open-state trapping and autoinhibition, such that two distinct mechanisms for cA

275 pports a model of reduced ability of regular autoinhibition, suggesting a gain of function mechanism

276 th profoundly different kinetics, undergoing autoinhibition (TBAT) or quasi-stochastic autoaccelerati

277 served and nondegenerate determinants of CBD autoinhibition that extends beyond the originally propos

278 timing of nuclear entry, or transcriptional autoinhibition, the phospho-occupancy at Ser826/Ser828 i

279 n of mitotic kinases that neutralizes Haspin autoinhibition through a mechanism dependent on multisit

280 subunit regulates activation, catalysis and autoinhibition through the a-loop.

281 by the protein kinase PknB or PknG triggers autoinhibition through the intramolecular association of

282 A common mechanism for formin regulation is autoinhibition, through interaction between the N-termin

283 B cell lymphoma somehow perturb ID-mediated autoinhibition to confer CARD11 with the dysregulated sp

284 nes and how membrane interactions unlock FAK autoinhibition to promote activation.

285 ains unclear how such binding events relieve autoinhibition to unmask the VCA segment and activate th

286 01/-02 and mDia2-DAD peptides, which disrupt autoinhibition, to examine the roles of mDia inactivatio

287 tol 4,5-bisphosphate and cargo relieves this autoinhibition, triggering clathrin recruitment and henc

288 d set of regulatory domains integrates basal autoinhibition, tyrosine kinase engagement, and addition

289 ll, Holderfield and colleagues show that RAF autoinhibition underpins this paradox, further complicat

290 ioC module is autoinhibited, with release of autoinhibition upon Galpha(q/11) binding.

291 ation of the F3 lobe is accomplished through autoinhibition via anti-parallel dimerization.

292 RC, possibly because it is not vulnerable to autoinhibition via molybdenum desulfuration.

293 icotinic receptors and tightly controlled by autoinhibition via muscarinic M2 receptors.

294 Autoinhibition was retro-engineered into a constitutivel

295 residues in the DNA recognition helix affect autoinhibition, we define a new function of ETS1 autoinh

296 We propose a novel, two-tier model of autoinhibition where the activation box and the molten g

297 Autoinhibition, where a segment of the protein covers it

298 Human dynein is regulated by autoinhibition, whereby intermolecular contacts limit mo

299 of this mechanism that we term "facilitated autoinhibition," whereby a complex consisting of cyclase

300 This mode of autoinhibition, which is not shared by the HECT domain l