ライフサイエンスコーパス: prodomain

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

2 critically dependent on the presence of the prodomain.

3 d the molecular chaperone activity of ADAM10 prodomain.

4 pecific ADAMDEC1-independent cleavage of the prodomain.

5 nd proteasomal degradation of the inhibitory prodomain.

6 nformation without the aid of a chaperone or prodomain.

7 ion triggers cleavage and degradation of the prodomain.

8 first removes the extreme C-terminus of the prodomain.

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

10 cellular matrix as a latent complex with its prodomain.

11 thologs revealed that CPO does not require a prodomain.

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

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

14 n be activated by cleavage of the associated prodomain.

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

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

17 ed via proteolytic removal of its inhibitory prodomain.

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

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

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

21 t unable to fold without assistance from its prodomain.

22 ncy of which is maintained by its inhibitory prodomain.

23 oteasomal degradation of the inhibitory Ssy5 prodomain.

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

25 bility of protease cleavage sites within the prodomain.

26 es a disordered N-terminal region in PCSK9's prodomain.

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

28 from the latency imposed by its surrounding prodomain.

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

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

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

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

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

34 eta and identify cleavage sites within their prodomains.

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

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

37 of the prodomain and that CtpA degrades the prodomain after a third, unidentified protease (P3) firs

38 The prodomain also catalyzes the late proline isomerizations

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

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

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

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

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

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

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

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

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

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

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

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

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

52 D1 and D2 in the prodomain and D'D3 in mature VWF at Golgi pH form helica

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

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

55 onsible for the regulated degradation of the prodomain and for creation of an intermediate polypeptid

56 orm) in solution leads to the release of the prodomain and formation of a sENG:BMP9 complex.

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

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

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

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

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

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

63 n is required to initiate degradation of the prodomain and that CtpA degrades the prodomain after a t

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 e BMP10:ALK1 complex at 2.3 angstrom and the prodomain-bound BMP9:ALK1 complex at 3.3 angstrom.

100 eric sENG with the circulating form of BMP9 (prodomain-bound form) in solution leads to the release o

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

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

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

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 Because ADAM prodomains can act as specific inhibitors, we postulate

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 Indeed, prodomain cleavage by meprin beta caused increased ADAM

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

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

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

116 metalloproteinases 9, 10, and 17 by specific prodomain cleavage.

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

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

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

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

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

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

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

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

125 formational epitope in the arm region of the prodomain distant from the proteolytic cleavage sites.

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

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

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

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

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

131 3 TGF-beta family members indicate a similar prodomain fold.

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

133 mics (MD) simulations of the 91 residue BDNF prodomain, for both the V66 and M66 sequence.

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

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

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

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

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

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

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

141 F) is generated by proteolytic cleavage of a prodomain from the proBDNF precursor either intracellula

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

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

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

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

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

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

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

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

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

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

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

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

154 e antibody occupy the two arm regions of the prodomain in the pro- and latent myostatin homodimers, s

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

179 lled FhaB, its C-terminal ~1,200 amino acid 'prodomain' is removed during translocation to the cell s

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

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

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

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

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

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

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

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

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

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

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

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

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

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

194 o a predicted amphipathic alpha-helix in the prodomain N terminus adopt helical structure in a membra

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

218 Prodomains of A disintegrin and metalloproteinase (ADAM)

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

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

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

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

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

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

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

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

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

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

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

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

231 Ptr3 have opposing roles in controlling Ssy5 prodomain phosphorylation.

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

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

234 Finally, prodomain processing is developmentally regulated in the

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

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

237 , the N-terminal acidic stretch of the PCSK9 prodomain (Q31-T60) has eluded structural investigation,

238 We show that the central prodomain region is required to initiate degradation of

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

240 The prodomain region was found to be intrinsically disordere

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

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

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

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

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

246 The prodomain remains tightly associated with the catalytic

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

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

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

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

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

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

253 0 (within the secondary cleavage site of the prodomain) (rs1799904) was studied.

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

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

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

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

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

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

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

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

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

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

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

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

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

267 The SAHP version of the BDNF prodomain suggested a protein segmented into three regio

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

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

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

271 zymogen inactivation, with CpaB serving as a prodomain that inhibits catalytically active CpaA.

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

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

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

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

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

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

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

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

280 nformation to active caspase-8, enabling its prodomain to engage ASC.

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

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

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

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

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

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

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

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

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

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

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

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

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