ライフサイエンスコーパス: prodomain

1 nformation without the aid of a chaperone or prodomain.

2 ion triggers cleavage and degradation of the prodomain.

3 P is maintained by its N-terminal inhibitory prodomain.

4 cellular matrix as a latent complex with its prodomain.

5 thologs revealed that CPO does not require a prodomain.

6 and then at an upstream site (S2) within the prodomain.

7 n, the latency of which is maintained by its prodomain.

8 at the mature ligand is not inhibited by the prodomain.

9 from the latency imposed by its surrounding prodomain.

10 n be activated by cleavage of the associated prodomain.

11 and then at an upstream site (S2) within the prodomain.

12 us mutations, Q170H and R181G, in the ADAM10 prodomain.

13 ed via proteolytic removal of its inhibitory prodomain.

14 act with either the C-terminal domain or the prodomain.

15 n an inactive, non-covalent complex with its prodomain.

16 ibits TACE with the same potency as TACE own prodomain.

17 t unable to fold without assistance from its prodomain.

18 ncy of which is maintained by its inhibitory prodomain.

19 y proteolytic cleavage of a large N-terminal prodomain.

20 T through the removal of its auto-inhibitory prodomain.

21 f both an intact intersubunit linker and the prodomain.

22 of forming a latent complex with its cleaved prodomain.

23 re BMP-4 after it has been released from the prodomain.

24 role in the intracellular removal of ADAMTS4 prodomain.

25 SUB1 at 2.25 A, in complex with its cognate prodomain.

26 nd its N-terminal latency-associated peptide prodomain.

27 ow as a major furin cleavage site within the prodomain.

28 critically dependent on the presence of the prodomain.

29 d the molecular chaperone activity of ADAM10 prodomain.

30 pecific ADAMDEC1-independent cleavage of the prodomain.

31 nd proteasomal degradation of the inhibitory prodomain.

32 ent, latent complexes with their SPC-cleaved prodomains.

33 s, MMPs become active after removal of their prodomains.

34 extracellular region of ADAM17 consists of a prodomain, a catalytic domain, a disintegrin domain, and

35 Overall, the results show that the prodomain acts as an intramolecular chaperone during ass

36 a model in which the intracellularly located prodomain affects the final conformation of the extracel

37 The prodomain also catalyzes the late proline isomerizations

38 mpassing the C-terminal glycine repeat and C-prodomain (amino acids 1000-1453) was affinity-labeled w

39 An N-terminal region of the PCSK9 prodomain (amino acids 31-52) was required for binding t

40 molecular folding reaction of the subtilisin prodomain and a series of subtilisin mutants, which were

41 een the thiol of a conserved cysteine in the prodomain and a zinc atom in the catalytic domain.

42 forms of BMP9 were capable of binding to the prodomain and ALK1, the M-form demonstrated less sustain

43 of chimeric precursors containing the BMP-7 prodomain and BMP-4 mature domain, or vice versa, with o

44 The BMP-7 prodomain and BMP-7 complex, but not the separated growt

45 possibility of interactions between the BMP1 prodomain and BMPs 2-7.

46 ndent manner and that co-incubation with the prodomain and catalytic domain had no effect on this bin

47 PCSK9 is self-processed to a complex of its prodomain and catalytic domain like a typical protein co

48 itor, the N-terminal domain (composed of the prodomain and catalytic domain) was not.

49 e active site, near the junction between the prodomain and catalytic domain, and inhibits MMP9 by two

50 ssed caspase-3 in a manner that required its prodomain and cleavage between its large and small subun

51 r a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activat

52 alpha(v) integrin to an RGD sequence in the prodomain and exertion of force on this domain, which is

53 It is unclear which prodomain and GF monomer are linked before proprotein co

54 utions affect well-conserved residues in the prodomain and in the peptidase domain of ADAMTS3.

55 series allows evaluation of the role of the prodomain and intersubunit linker on caspase-6 structure

56 alytic activity of purified ADAM17 lacking a prodomain and its intracellular region is diminished und

57 n convertase cleavage sites; two between the prodomain and ligand domain, which we call the Main and

58 ght on the functional role of the inhibitory prodomain and on the proteolytic control of MT1-MMP acti

59 s-331 of GARP disulfide link to the TGFbeta1 prodomain and that GARP with C192A and C331A mutations c

60 racts specifically with a signal in the BDNF prodomain and that perturbations in BDNF trafficking may

61 covalent latent complex with its SPC-cleaved prodomain and that this latent complex is activated via

62 A truncated version of PCSK9 containing the prodomain and the catalytic domain, but not the C-termin

63 al and the degradation of the autoinhibitory prodomain and the liberation of the functional activity

64 Cleaved caspase-6 with both the prodomain and the linker present is the most stable, ind

65 quired for the degradation of the inhibitory prodomain and the release of the activated, mature MT1-M

66 s for force application through the TGF-beta prodomain and through the beta- and not alpha-subunit of

67 ation by mediating the proximity of the Ssy5 prodomain and Yck1/2.

68 ively co-immunoprecipitates with the cleaved prodomain and/or precursor form of TGF-beta family membe

69 a ring-shaped complex, a novel fold for the prodomain, and show how the prodomain shields the growth

70 only functional in the context of the BMP-4 prodomain, and that differential cleavage around this do

71 -human ADAM8 polyclonal antibody against its prodomain, and the ADAM8 levels were measured by an enzy

72 hen reassembly occurs in the presence of the prodomain, and this effect is specific for the propeptid

73 ursor (pro-TGF-beta1), integrins bind to the prodomain, apply force, and release the TGF-beta growth

74 that sequences within the N-terminus of the prodomain are required for this intracellular localizati

75 ts, although levels of precursor and cleaved prodomain are unchanged compared with wild type.

76 We conclude that TACE and ADAM 10 prodomains are functionally equivalent in a way that sep

77 functional excess and that C- and N-terminal prodomains are removed successively, following its depos

78 r monomer in the dimeric structure (i.e. the prodomain arm domain and GF domain in each monomer are s

79 ion, and model building demonstrate that the prodomain arm domain in one monomer is linked to the GF

80 These results identify the Met66 prodomain as a new active ligand, which modulates neuron

81 generated by stripping off the tightly bound prodomain at pH 2.1.

82 l autocatalytic processing of its N-terminal prodomain at sites B'/B followed by the herein newly ide

83 has autocatalytic activity that releases the prodomain at the N terminus of the protein.

84 roprotein convertase cleaving the inhibitory prodomain at the R108RKR111 downward arrowY112 site, whe

85 used the cells that expressed the wild-type prodomain-based fluorescent biosensor and the mutant bio

86 ibitors of metalloproteinases and a specific prodomain-based inhibitor of ADAM10 perturb the release

87 re determined in order to understand how the prodomain binding affects the energetics of subtilisin f

88 Prodomain binding results in high protection factors (10

89 acceleration of exchange in these regions by prodomain binding reveals an antagonism between the fold

90 Overall, prodomain binding seems to facilitate the organization o

91 onfirmed these findings and also showed that prodomain binding targets the growth factor to fibrillin

92 Together, these data show that upon prodomain binding to fibrillin-1, the BMP-7 complex unde

93 e major intermediate, which is stabilized by prodomain binding, independent of metal concentration an

94 cost of stability in regions more distal to prodomain binding: the C-terminal alpha-helix H and the

95 Here we demonstrate that the BMP1 prodomain binds BMPs 2 and 4 with high specificity and w

96 A hydrophobic residue in the prodomain binds to a pocket adjacent to the alpha7-helix

97 vitro and in vivo, and that endogenous BMP1 prodomain-BMP4 complexes exist in cell culture media and

98 ity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent.

99 secreted from mouse right atrium was in the prodomain-bound form.

100 t cysteine proteases, FP2 does not require a prodomain but only the short FP2(nose) motif to correctl

101 ADAMTS7B undergoes removal of the prodomain by a multistep furin-dependent mechanism.

102 inhibitory phosphorylation of the caspase-2 prodomain by activated Ca(2+)/calmodulin-dependent prote

103 fibrillogenesis, and that processing of the prodomain by BMP-1 potentiates the ability of OGN to mod

104 on the signal-induced phosphorylation of its prodomain by casein kinase I (Yck1/2).

105 site followed by the release of the degraded prodomain by furin cleavage that finalizes the two-step

106 SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature

107 Fusion proteins tagged with the engineered prodomain can be bound to the column and washed free of

108 prodomain, in contrast to BMP-4, -5, and -7 prodomains, can inhibit the bioactivity of the BMP-10 gr

109 ously Dronc) cleaves and activates two short-prodomain caspases, Dcp-1 and Ice (previously Drice), su

110 late-onset Alzheimer's disease by impairing prodomain chaperone function, attenuating alpha-secretas

111 ity by depleting surface ProN levels through prodomain cleavage by an exogenous protease.

112 Our findings demonstrate that BMP prodomain cleavage ensures that the mature ligand is not

113 Signal sequence and prodomain cleavage in the ER and Golgi apparatus, respec

114 the Ser-to-Pro substitution affected ADAMTS7 prodomain cleavage.

115 hange rates of 223 amide protons in free and prodomain-complexed subtilisin were determined in order

116 Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC r

117 mordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment

118 idered an initiator caspase because its long prodomain contains a CARD domain that allows its recruit

119 uggest that intrinsic properties of the BMP4 prodomain contribute to the relative bioactivities of ho

120 The prodomains death effector domains (DEDs) of caspase 8 we

121 Crystal structure of a prodomain-deleted Dronc zymogen, determined at 2.5 A res

122 n this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in mu

123 vage sites precludes caspase-8 activation by prodomain-driven dimerization.

124 eptides of 14-26 aa derived from the cleaved prodomain during activation.

125 s protein phosphatase 2A activity toward the prodomain, effectively setting a signaling threshold req

126 ubstrate is based on a stabilized subtilisin prodomain, extended across the active site by the additi

127 The data show that the prodomain facilitates both dimerization and active-site

128 3 TGF-beta family members indicate a similar prodomain fold.

129 In the presence of the prodomain, folding proceeds through one major intermedia

130 liberates a small, evolutionarily conserved, prodomain fragment (the linker peptide) of unknown fate

131 Swapping the prodomain fragments between fly and human resulted in a

132 ose catalytic domain remains associated with prodomain fragments of different lengths.

133 quence and mass spectrometry analysis of the prodomain fragments, we demonstrated that the intradomai

134 ed to generate both the bioactive ligand and prodomain fragments, which lack signaling activity.

135 essing in the Golgi to cleave the N-terminal prodomain from the C-terminal growth factor (GF) domain

136 Removal of the prodomain from the precursor did not interfere with co-t

137 provides insights into which regions of the prodomain-GF complex are highly structurally conserved a

138 s were used to map the critical epitopes for prodomain-growth factor and prodomain-prodomain binding.

139 present the nanoscale structure of the BMP-7 prodomain-growth factor complex using electron microscop

140 imer in an inactive complex; for others, the prodomain.growth factor complex is active, even though t

141 In addition, biochemical studies of prodomain.growth factor complexes were performed to iden

142 actor-8 (GDF-8), which are known to exist in prodomain/growth factor complexes.

143 n a valine to methionine substitution in the prodomain, has been shown to lead to defective regulated

144 ons are poorly defined, and functions of the prodomains have been largely ignored.

145 In particular, mutant GDF11 prodomains impervious to cleavage by BMP1/Tolloid protei

146 ynthesized as larger precursors containing a prodomain in addition to an N-terminal signal peptide.

147 a reduction in the amount of cleaved ADAMTS7 prodomain in media conditioned by VSMCs of the G/G genot

148 previously unknown requirement for the BMP4 prodomain in promoting heterodimer activity.

149 After cleavage, PCSK9 retains its prodomain in the active site as a self-inhibitor.

150 Results show that the BMP-10 prodomain, in contrast to BMP-4, -5, and -7 prodomains,

151 (NMR), revealing that it mimics a subtilisin prodomain including a flexible C-terminal peptide that m

152 y, application of Met66 (but not Val66) BDNF prodomain induces acute growth cone retraction and a dec

153 Sequence determinants for TACE prodomain inhibition of the catalytic domain are yet to

154 n those regions as key determinants for TACE prodomain inhibitory function.

155 In cell-based assays we show that the ADAM10 prodomain inhibits betacellulin shedding, demonstrating

156 the interaction of Hsp27 with the caspase-3 prodomain inhibits the second proteolytic cleavage neces

157 The conformation of the prodomain integrin-binding motif differs in the presence

158 Moreover, the mouse ADAM10 prodomain is a selective inhibitor as it only weakly inh

159 In addition, we show that the BMP4 prodomain is both necessary and sufficient for generatio

160 It is further demonstrated that the BMP1 prodomain is capable of modulating signaling by BMPs 2 a

161 Here we show that the isolated BDNF prodomain is detected in the hippocampus and that it can

162 the PGD downward arrow L(50) sequence of the prodomain is essential for the protumorigenic function o

163 ion between alpha(v)beta(6) integrin and the prodomain is insufficient for TGF-beta1 release.

164 opy and circular dichroism, we find that the prodomain is intrinsically disordered, and the Val66Met

165 We hypothesized that the Gbb prodomain is involved not only in regulating the product

166 The binding site for the GDF-8 prodomain is likely the heparan sulfate chain present on

167 This antagonism helps to explain why the prodomain is needed to stabilize the folding intermediat

168 For some members of the superfamily, the prodomain is noncovalently associated with its growth fa

169 th factor complex is active, even though the prodomain is noncovalently associated with its growth fa

170 Although it is known that the FhaB prodomain is required for FHA function in vivo, its role

171 We show here that the FhaB prodomain is required for the extracellularly located ma

172 We show that the C-terminus of the prodomain is retained intracellularly and that sequences

173 es, indicating that ADAM10 inhibition by its prodomain is unique.

174 Instead of the consensus MMP prodomain, it features a 14-residue propeptide, the shor

175 natural substrate, and interaction with the prodomain, its natural inhibitor.

176 , P49/P35-resistant protease and then at the prodomain junction DHTD(28)-A by a P49/P35-sensitive pro

177 ex (LLC) in which it is bound to its cleaved prodomain (latency-associated peptide [LAP]) and, via LA

178 ltimerizes and autocatalytically removes the prodomain leading to the formation of the active, proces

179 ses premature release of the ligand from the prodomain, leading to destabilization of the ligand and

180 uclear caspase-2 at the S122 site within its prodomain, leading to its cleavage and activation.

181 ysis supports a model in which the transient prodomain/ligand complex that forms during sequential cl

182 which generates a non-covalently associated prodomain/ligand complex that is subsequently dissociate

183 , showing that functional differences in the prodomain limit the BMP7 activity in flies.

184 A large 151-residue C-shaped prodomain makes extensive contacts as it wraps around th

185 more, TSPAN12 overexpression enhanced ADAM10 prodomain maturation, whereas TSPAN12 ablation diminishe

186 quential cleavage plays an essential role in prodomain-mediated stabilization of the mature ligand un

187 Neuron, Suh et al. describe two rare ADAM10 prodomain mutations that cause late-onset Alzheimer's di

188 pha-secretase activity, owing to LOAD ADAM10 prodomain mutations, leads to AD-related pathology, stro

189 s of the CPA subfamily contain an N-terminal prodomain necessary for folding, bioinformatics and expr

190 he inactivation of the respective inhibitory prodomains not only for MT1-MMP but also for other MMP f

191 tic domain, and the C-terminal Gln152 of the prodomain occupies the active site like a substrate for

192 In contrast, the prodomain of ADAM 9 inhibited TACE only weakly.

193 proteolytic activity, demonstrating that the prodomain of ADAMDEC1, like in other members of the ADAM

194 ing that furin physically interacts with the prodomain of ADAMTS-4.

195 ecent studies have shown that removal of the prodomain of ADAMTS4 is critical for its ability to degr

196 ine (Met) substitution at position 66 in the prodomain of BDNF (Val66Met)], a genetic mutation shown

197 an intracellular chaperone that binds to the prodomain of BDNF to traffic it to the regulated secreto

198 Results show that the prodomain of BMP-5 interacts with the N-terminal regions

199 molecules homologous to the fibrillins, the prodomain of BMP-7 was tested for binding to fibrillin-1

200 in (vFLIP), called K13, with homology to the prodomain of caspase 8.

201 on of endogenous Apaf-1 with the recombinant prodomain of caspase 9, it did not affect the associatio

202 raction between Hsp27 and the amino-terminal prodomain of caspase-3.

203 10FP2 was poorly inhibited by the inhibitory prodomain of FP2.

204 However, in contrast, the prodomain of GDF-8 (myostatin) interacts with the glycos

205 enetic protein-7 (BMP-7) are mediated by the prodomain of growth factor complexes.

206 D-Ala carboxypeptidase and to the N-terminal prodomain of human metalloproteinases that act on extrac

207 ation of MMP-1 and -13, which can cleave the prodomain of MMP-9.

208 pendent, channel-modulating function for the prodomain of MMP23 (MMP23-PD).

209 Our in silico modeling suggests that the prodomain of MT1-MMP exhibits a conserved three helix-bu

210 ith the intracellular domain of CD95 and the prodomain of procaspase-8 and reveal a self-association

211 The unprocessed prodomain of Scw(E1) remains in a complex with the Dpp:S

212 Because the prodomain of TGFbeta interacts with latent TGFbeta-bindi

213 single nucleotide polymorphism (SNP) in the prodomain of the BDNF gene.

214 two rare mutations (Q170H and R181G) in the prodomain of the metalloprotease, ADAM10, that cosegrega

215 leading to a Ser-to-Pro substitution in the prodomain of the protease ADAMTS7.

216 Prodomains of A disintegrin and metalloproteinase (ADAM)

217 latent TGFbeta-binding proteins and between prodomains of BMP-2, -4, -7, and -10 and GDF-5 and fibri

218 The prodomains of falcipain-2 and falcipain-3 were sufficien

219 In addition, they raise the possibility that prodomains of other TGFbeta-like growth factors interact

220 Mouse prodomains of TACE and ADAM8 do not inhibit their respec

221 The specific functions of the prodomains of TGFbeta superfamily members are largely un

222 Interactions are known between prodomains of TGFbeta-1-3 and latent TGFbeta-binding pro

223 These studies suggest that the prodomains of TGFbeta-like growth factors are important

224 lins may mediate interactions with all other prodomains of this superfamily.

225 rs to subtilisin folding and to show how the prodomain overcomes these barriers.

226 n approaches to investigate the roles of the prodomain (PD) and the C-terminal domain (CD) and its mo

227 actor-beta-like growth factor complexes, the prodomain (pd) confers latency to the complex.

228 d by the Ssy1 receptor to dynamically induce prodomain phosphorylation by mediating the proximity of

229 Ptr3 have opposing roles in controlling Ssy5 prodomain phosphorylation.

230 We propose that the hydrophobic N-terminal prodomain plays an early and essential role in aligning

231 The mouse ADAM9 prodomain (proA9; amino acids 24-204), expressed and cha

232 on motif, whereas the cytoplasmic domain and prodomain processing are not required for the rapid acti

233 Finally, prodomain processing is developmentally regulated in the

234 cal epitopes for prodomain-growth factor and prodomain-prodomain binding.

235 dimer noncovalently associated with its two prodomain propeptide chains and that the BMP-7 complex i

236 we report that the recombinant mouse ADAM10 prodomain, purified from Escherichia coli, is a potent c

237 orphogenetic proteins (BMPs) 2-7, and to the prodomain region of the metalloproteinase BMP1.

238 The prodomain region was found to be intrinsically disordere

239 sults in a Val66Met substitution in the BDNF prodomain region.

240 n by furin was considered sufficient for the prodomain release and MT1-MMP activation.

241 rmined, however, that the full-length intact prodomain released by furin alone is a potent autoinhibi

242 The intact prodomain released by furin alone, however, is a potent

243 nd secretion, whereas constructs lacking the prodomain remained in the cytosol.

244 The prodomain remains tightly associated with the catalytic

245 h, arguing against a major role of increased prodomain removal in the rapid stimulation of ADAM10.

246 Absence of cleavage of the prodomain renders Adam17(Delta252-281) functionally inac

247 dence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functi

248 s prior to or following the removal of their prodomains, respectively.

249 s expressed as a zymogen, and removal of the prodomain results in its activation.

250 Detailed analysis of ADAM prodomains revealed two short regions for which TACE and

251 0 (within the secondary cleavage site of the prodomain) (rs1799904) was studied.

252 Using mutagenesis of the prodomain sequence and mass spectrometry analysis of the

253 Additional MMP cleavages within the prodomain sequence are required to release the MT1-MMP e

254 on, the R(108)RKR(111) downward arrow Y(112) prodomain sequence is processed by furin.

255 -R-P-R-C(93) and R(108)-R-K-R-Y(112), in the prodomain sequence of MT1-MMP.

256 MT1-MMP requires proteolytic removal of the prodomain sequence.

257 y members are synthesized as precursors with prodomain sequences that are proteolytically removed by

258 Co-purification of BMPs 2-7 with BMP1 prodomain sequences through the multiple biochemical ste

259 that PDGFs share a conserved region in their prodomain sequences which can remain noncovalently assoc

260 Although His-69 within the furin prodomain serves as the pH sensor that detects transport

261 vel fold for the prodomain, and show how the prodomain shields the growth factor from recognition by

262 The D1-D2 prodomain shows 2 large connected assemblies, each conta

263 t a brain-derived neurotrophic factor (BDNF) prodomain single nucleotide polymorphism resulting in a

264 The Asn-67 and Asn-91 prodomain sites contained high mannose, whereas complex

265 eous rather than sequential cleavage of both prodomain sites show loss of BMP4 function and die durin

266 he emerging concept that TGFbeta superfamily prodomains target their growth factor dimers to extracel

267 signaling and demonstrate differences in how prodomains target their growth factors to the extracellu

268 C-terminal cytokine domain and an N-terminal prodomain that are cleaved by caspase-3.

269 tation at the furin cleavage site within the prodomain that is crucial for ligand production.

270 eine peptidase, reveals a novel fold for the prodomain that is distantly related to sugar-binding lec

271 h the exoprotein contains a large C-terminal prodomain that is removed during translocation.

272 not be cleaved remains in a complex with the prodomain that is targeted for lysosomal degradation, an

273 c domain containing a zinc ion, as well as a prodomain that regulates enzyme activation by modulation

274 amily domain, and its 205-residue N-terminal prodomain, the largest structurally characterized to dat

275 e) share only 23% sequence identity at their prodomains, the latter in isolation inhibits TACE with t

276 ones in which sorting is directed by ordered prodomains, the sorting determinants of proglucagon lie

277 the S2 site liberates mature BMP-4 from the prodomain, thereby stabilizing the protein.

278 ecretion is controlled by the ability of its prodomain to facilitate autocleavage, whereas human MMP1

279 sequentially cleaved at two sites within the prodomain to generate an active ligand.

280 hown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling

281 TR) and differential engagement of the Met66 prodomain to the SorCS2 receptor are required for this e

282 Our study reveals a novel function of prodomains to enable import of small or intrinsically di

283 xperiments revealed that the activity of the prodomains to promote productive ER import resides in th

284 Here we expressed the prodomain together with a catalytically inactive proteas

285 ed a stable form of the auto-inhibitory TACE prodomain (TPD), which specifically inhibits in vitro an

286 Proteolytic processing of the prodomain transforms the zymogen into a catalytically ac

287 ATP nor FDNP-ATP exhibits any effect on the prodomain-truncated enzyme DeltaproCsp9 or p18/p10.

288 Evidence suggests that the prodomain undergoes intradomain cleavage at the PGD down

289 We prepared TACE prodomain variants containing full or partial switches t

290 BMP-7 prodomain variants were used to map the critical epitope

291 fic, processing protease, and the subtilisin prodomain was coengineered into an optimized recognition

292 Third, the subtilisin prodomain was engineered to direct cleavage to the junct

293 the AtMC1 catalytic site, and that the AtMC1 prodomain was not required for the interaction.

294 pains, which include large membrane-spanning prodomains, we utilized chimeras with portions of the pr

295 f the cytoplasmic portion of the falcipain-2 prodomain were required for efficient food vacuolar traf

296 ia the Arg-Gly-Asp (RGD) motif in the enzyme prodomain, which regulated interactions with integrins a

297 he Main and Shadow sites, and one within the prodomain, which we call the Pro site.

298 olytic removal of their N-terminal dipeptide prodomains while a significant portion of granzyme C is

299 s a signal peptide, a 60-90-residue globular prodomain with a conserved sequence motif including a cy

300 age increased association of the full-length prodomain with Gbb15, resulting in a concomitant decreas