ライフサイエンスコーパス: MASP

1 MASP-1 activates MASP-2 and, moreover, inhibition of MAS

2 MASP-1 and MASP-3 are related proteases found in similar

3 MASP-1 has been shown to aid MASP-2 convertase generatio

4 MASP-1 protein was immunochemically localized to synovia

5 MASP-1 transactivates MASP-2 and, although MASP-1 also c

6 MASP-1 was recently found to be the exclusive activator

7 MASP-1 was shown to cleave high m.w. kininogen into brad

8 MASP-2 cleaves C4 releasing C4a and generating C4b, whic

9 MASP-2 deficiency also protects mice from gastrointestin

10 MASP-2 is considered as the autonomous pathway-activator

11 MASP-2 was co-purified with H-ficolin, and the purified

12 MASP-3, which does not autoactivate, is also cleaved by

13 MASPs have a modular structure consisting of an N-termin

14 g lectin (MBL)-associated serine protease-1 (MASP-1) and MASP-3 contain zymogenic FD (pro-FD), and it

15 ficolin-associated serine protease (MASP)-1, MASP-2, and MASP-3 from the MBL complex.

16 led MBL-associated serine proteases (MASP-1, MASP-2, and MASP-3).

17 ation kinetics using purified active MASP-1, MASP-2, MASP-3, as well as thrombin.

18 L or ficolins allows the formation of MASP-1-MASP-2 co-complexes.

19 tiated by the C1r/C1s (classical) and MASP-1/MASP-2 (lectin) proteases.

20 binding lectin-associated serine protease 2 (MASP-2) has been described as the essential enzyme for t

21 mplex with MBL-associated serine protease 2 (MASP-2) was able to activate the lectin pathway and depo

22 olins with MBL-associated serine protease-2 (MASP-2) and C1q with C1r and C1s.

23 binding lectin-associated serine protease-2 (MASP-2) on the mutant.

24 binding lectin-associated serine protease-2 (MASP-2), and analyzed the role of MASP-2 in two models o

25 d activate MBL-associated serine protease-2 (MASP-2).

26 netics using purified active MASP-1, MASP-2, MASP-3, as well as thrombin.

27 annose-binding lectin associated-protease-3 (MASP-3) is a member of the lectin pathway of the complem

28 The serum levels of ficolin-2, ficolin-3, MASP-2, ficolin-3/MASP-2 complex, C1-INH, and C4, as wel

29 Levels of MASP-2 and of the ficolin-3/MASP-2 complex were elevated (P < .0001 and .033, respec

30 s of ficolin-2, ficolin-3, MASP-2, ficolin-3/MASP-2 complex, C1-INH, and C4, as well as the extent of

31 nctional unit for complement activation is a MASP homodimer bound to two MBP trimeric subunits.

32 The role of the much more abundant MASP-1 protease was controversial.

33 MASP-1 activates MASP-2 and, moreover, inhibition of MASP-1 prevents auto

34 canonical inhibitor developed against active MASP-1, indicating that zymogen MASP-1 fluctuates betwee

35 , we found that lack of enzymatically active MASP-3, or complete MASP-3 deficiency, compromises the c

36 activators in resting blood; however, active MASP-3 is a very likely physiological activator.

37 ts activation kinetics using purified active MASP-1, MASP-2, MASP-3, as well as thrombin.

38 sing unique, monospecific inhibitors against MASP-1 and MASP-2, we corrected the mechanism of lectin-

39 MASP-1 has been shown to aid MASP-2 convertase generation by auxiliary C2 cleavage.

40 MASP-1 transactivates MASP-2 and, although MASP-1 also cleaves C2, MASP-2 cleaves both C4 and C2, a

41 We show that, although MASP-2 is able to autoactivate under artificial conditio

42 In this study, we demonstrate that, although MASPs do not directly form heterodimers, the addition of

43 Complexes containing both MAP-1 and MASP-1 or -3 were detected in normal human serum and pla

44 The levels of MASP-1 and MASP-1/C1-INH complexes are reduced in HAE patients comp

45 Both MASP-1 and MASP-1/C1-INH complexes are related to the degree of com

46 The level of MASP-1 and MASP-1/C1-INH complexes in HE patients correlated with t

47 functional terms, it appears that MASP-1 and MASP-2 act in a manner analogous to that of C1r and C1s

48 s recently demonstrated that both MASP-1 and MASP-2 are crucial to lectin pathway activation.

49 f the classical pathway, in which MASP-1 and MASP-2 are found together in the same MBL or ficolin com

50 We further demonstrate that MASP-1 and MASP-2 can associate in the same MBL complex, and that s

51 Combining our quantitative data, MASP-1 and MASP-2 can be ruled out as direct pro-FD activators in r

52 MBL-associated serine proteases (MASP)-1 and MASP-2 cleave C4 and C2 to generate C3 convertase.

53 Juxtaposition of MASP-1 and MASP-2 during activation must be required for transactiv

54 haelis-like complex structures of MASP-1 and MASP-2 formed with substrate-like inhibitors.

55 ur previously developed selective MASP-1 and MASP-2 inhibitors did not reduce pro-FD activation at re

56 es that binding to both truncated MASP-1 and MASP-2 proteins is defective in such mutants.

57 le cross-activation steps between MASP-1 and MASP-2 were determined.

58 MBL)-associated serine proteases, MASP-1 and MASP-2, have been thought to autoactivate when MBL/ficol

59 , monospecific inhibitors against MASP-1 and MASP-2, we corrected the mechanism of lectin-pathway act

60 mplement pathway serine proteases MASP-1 and MASP-2.

61 MASP-1 and MASP-3 are related proteases found in similar complexes.

62 It was suggested that MASP-1 and MASP-3 directly activate pro-FD; however, other experime

63 In mice, MASP-1 and MASP-3 have been reported to be central also to alternat

64 tigated the direct interactions of MAP-1 and MASP-3 with ficolin-3 and MBL using surface plasmon reso

65 y (collectin kidney 1 (CL-K1) and MASP-1 and MASP-3, respectively).

66 unaffected by reconstitution with MASP-1 and MASP-3.

67 gene and hence deficient in both MASP-1 and MASP-3.

68 L)-associated serine protease-1 (MASP-1) and MASP-3 contain zymogenic FD (pro-FD), and it is becoming

69 lative effects of inhibiting both MASP-2 and MASP-1 have a greater effect on the lectin pathway than

70 ciated serine protease (MASP)-1, MASP-2, and MASP-3 from the MBL complex.

71 ciated serine proteases (MASP-1, MASP-2, and MASP-3).

72 o and was associated with both MASP-1/-3 and MASP-2 in plasma.

73 Both ficolin-3 and MASP-2 levels correlated inversely with the time from th

74 inhibitor blocks the active sites of C1s and MASP-2, as well as the anion-binding exosites of the enz

75 iant Amazon leech, potently inhibits C1s and MASP-2, whereas it is also a good inhibitor of MASP-1.

76 n vitro and shown to require MASP-2, C2, and MASP-1/3.

77 Mutations in C4 and MASP-2 residues at the C345C-CCP interface inhibit the i

78 are initiated by the C1r/C1s (classical) and MASP-1/MASP-2 (lectin) proteases.

79 biological properties both MAP (CsMAP34) and MASP (CsMASP1) molecules from tongue sole (Cynoglossus s

80 localization of mRNA and protein for FD and MASP-1/3 in synovial adipose tissue (SAT) and fibroblast

81 ment pathway (collectin kidney 1 (CL-K1) and MASP-1 and MASP-3, respectively).

82 on of immune complexes (ICs) containing anti-MASP SP IgGs in patients with different (cardiac, digest

83 perimental model suggest the utility of anti-MASP-2 antibody therapy in reperfusion injury and other

84 rized the naturally occurring 3MC-associated MASP-3 mutants and found that they all yielded enzymatic

85 olving the lectin pathway and its associated MASPs.

86 of MASP-1 and the complex formation between MASP-1 and C1-INH were significantly reduced in HAE pati

87 d, we have analyzed the interactions between MASP-2, C4, C2, and their activation fragments and have

88 the possible cross-activation steps between MASP-1 and MASP-2 were determined.

89 Both MASP-1 and MASP-1/C1-INH complexes are related to the de

90 ity was confirmed in mice deficient for both MASP-2 and C4 (n=7), where the protection from postopera

91 f the MASP1 gene and hence deficient in both MASP-1 and MASP-3.

92 at the cumulative effects of inhibiting both MASP-2 and MASP-1 have a greater effect on the lectin pa

93 nvestigators recently demonstrated that both MASP-1 and MASP-2 are crucial to lectin pathway activati

94 range in vitro and was associated with both MASP-1/-3 and MASP-2 in plasma.

95 Binding studies reveal that both MASPs associate independently with rat MBP in a Ca(2+)-d

96 investigate whether activation of MASP-2 by MASP-1 occurs through PRM-driven juxtaposition on ligand

97 ch does not autoactivate, is also cleaved by MASP-1 quite efficiently.

98 C2 binds to C4b and is also cleaved by MASP-2 to form the C3 convertase (C4b2a).

99 ng that cleavage of pro-FD into mature FD by MASP-1 occurred on the CMP.

100 3 supernatants was cleaved into mature FD by MASP-1/3 in FLS supernatants.

101 ciated serine protease (MASP)-2, followed by MASP-2 autoactivation and cleavage of C4 and C2 generati

102 The perovskite films produced by MASP exhibit excellent optoelectronic properties with ef

103 nal lectin pathway, which can be restored by MASP-1, implying that this component is crucial for comp

104 This C4-bypass MASP-2 activity was confirmed in mice deficient for both

105 MASP-2 and, although MASP-1 also cleaves C2, MASP-2 cleaves both C4 and C2, allowing formation of the

106 s of the 203-kDa human C4 and the 245-kDa C4.MASP-2 substrate.enzyme complex.

107 We propose that the C4b.MASP-2 interaction favors attachment of C4b near to the

108 their activation fragments and have compared MASP-2-catalyzed cleavage of C4b2 and C2.

109 of enzymatically active MASP-3, or complete MASP-3 deficiency, compromises the conversion of pro-FD

110 to autoactivate under artificial conditions, MASP-1 dramatically increases lectin pathway activity at

111 Combining our quantitative data, MASP-1 and MASP-2 can be ruled out as direct pro-FD acti

112 as restored when rMASP-1 was added to either MASP-1/-3 KO sera or rhMBL.

113 d MASP-1 serum concentrations and endogenous MASP-1/C1-INH complex levels in 128 HAE patients and 100

114 We have also engineered MASP binding into a pulmonary surfactant protein (SP-A),

115 Relatively high levels of pre-existing MASP-1/C1-INH complexes were observed in normal serum, a

116 t, while also highlighting that there exists MASP-3-independent pro-FD maturation in 3MC patients.

117 d with H-ficolin, and the purified H-ficolin.MASP-2 complex could activate complement as measured by

118 een thought to autoactivate when MBL/ficolin.MASP complexes bind to pathogens triggering the compleme

119 is crucial for the activation of MBL/ficolin.MASP complexes, and in the proenzymic phase zymogen MASP

120 However, the molecular basis for MASP-3 function remains to be understood.

121 n MBL conserved lysine residue essential for MASP binding (K55) abolished binding to soluble CR1 and

122 Analogous mutants were made for MASP-2, and rate constants of the autoactivation steps a

123 e AP activity is still observed in sera from MASP-1/3-deficient Malpuech-Michels-Mingarelli-Carnevale

124 coated with anti-collagen mAb and serum from MASP-1/3(-/-) mice as a source of factor B, pro-FD in 3T

125 meostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown.

126 n this investigation, we identified immature MASP proteins containing the MASP SP in EVs secreted by

127 In MASP-2, an exosite located within the CCP domains recogn

128 Mutations in MASP-3 have recently been found to be associated with Ca

129 (control group), WT grafts transplanted into MASP-2-deficient recipients (n=7) showed significantly b

130 In a model of transient myocardial IRI, MASP-2-deficient mice had significantly smaller infarct

131 sting of glycan-bound mannan-binding lectin, MASP-2, and C4 is discussed.

132 than the zymogen state is default in lectin.MASP complexes and must be inhibited through additional

133 MBL-deficient individuals when exogenous MBL-MASP was added.

134 th and without the addition of exogenous MBL-MASP.

135 s disease patients have an impairment in MBL-MASP functional activity and that this defect is associa

136 icantly correlated with an impairment in MBL-MASP functional activity.

137 iologic (24 microg/ml) concentrations of MBL-MASP partially overcame the effects of inhibitors (57% k

138 ctin-mannose-associated serine protease (MBL-MASP) functional activity in Crohn's disease patients.

139 We conclude that MBL-MASP makes a major contribution to complement-mediated h

140 Preopsonization with MBL-MASP at concentrations as low as 0.03 microg/ml resulted

141 epleted serum (MBLdS) reconstituted with MBL-MASP before incubation with organisms (postopsonization)

142 pha(2)-macroglobulin added together with MBL-MASP, all at physiologic concentrations before adding MB

143 gnificant increases in phagocytosis with MBL-MASPs that were independent of complement activation.

144 attachment of C4b near to the activating MBL.MASP complex on the bacterial surface so that, following

145 blood aggregation demonstrated increased MBL/MASP complex-dependent platelet aggregation.

146 n together, these findings indicate that MBL/MASP complexes, and specifically MASP-1, play a key role

147 ce, suggesting a significant role of the MBL/MASP complex for in vivo coagulation.

148 In vitro, MBL/MASP complexes were captured on mannan-coated plates, an

149 We measured MASP-1 serum concentrations and endogenous MASP-1/C1-INH

150 In mice, MASP-1 and MASP-3 have been reported to be central also

151 We evolved a pair of monospecific MASP inhibitors.

152 higher, and the autocatalytic activation of MASP-1 is about 140-fold faster than those of MASP-2.

153 pted us to investigate whether activation of MASP-2 by MASP-1 occurs through PRM-driven juxtaposition

154 ical conditions through direct activation of MASP-2.

155 ently found to be the exclusive activator of MASP-2 under physiological conditions, yet the predomina

156 the absolute requirement for the activity of MASP-1 protein in autoimmune-associated inflammatory tis

157 Analysis of MASP binding by rat MBP containing naturally occurring m

158 In summary, autoactivation of MASP-1 is crucial for the activation of MBL/ficolin.MASP

159 ibition of MASP-1 prevents autoactivation of MASP-2.

160 t, not simply by brute force displacement of MASP-2 from MBL or ficolins, but by disruption of co-com

161 usion (IR) injury, we assessed the effect of MASP-2 deficiency in an isogenic mouse model of renal tr

162 The therapeutic effects of MASP-2 inhibition in this experimental model suggest the

163 P was not sufficient, because elimination of MASP, but not C1q, prevented TER reduction.

164 n of MBL or ficolins allows the formation of MASP-1-MASP-2 co-complexes.

165 ogether, these insights into the function of MASP-3 reveal how a mutation in this enzyme causes it to

166 ctivates MASP-2 and, moreover, inhibition of MASP-1 prevents autoactivation of MASP-2.

167 SP-2, whereas it is also a good inhibitor of MASP-1.

168 ntestinal IRI, as do mAb-based inhibitors of MASP-2.

169 Juxtaposition of MASP-1 and MASP-2 during activation must be required for

170 The level of MASP-1 and MASP-1/C1-INH complexes in HE patients correl

171 The levels of MASP-1 and MASP-1/C1-INH complexes are reduced in HAE pa

172 , and we found that both the serum levels of MASP-1 and the complex formation between MASP-1 and C1-I

173 Levels of MASP-2 and of the ficolin-3/MASP-2 complex were elevated

174 In order to investigate the mechanisms of MASP activation by MBP, the cDNAs of rat MASP-1 and -2 h

175 e of the zymogen form of the G666E mutant of MASP-3.

176 However, the necessity of MASP-3 for pro-FD cleavage has been questioned, because

177 binding to mannan or DNA in the presence of MASP-2, the CL-L1-CL-K1 complex mediated deposition of C

178 sized that MASP-1 levels and the quantity of MASP-1/C1-INH complexes might be associated with differe

179 The zymogen autoactivation rate of MASP-1 is approximately 3000-fold higher, and the autoca

180 rotease-2 (MASP-2), and analyzed the role of MASP-2 in two models of postischemic reperfusion injury

181 In accordance with the key role of MASP-2, the MASP-2 inhibitor completely blocks the lecti

182 ings reveal a new route for the secretion of MASP proteins in T. cruzi, which uses EVs as vehicles fo

183 esidue into the P2 of the activation site of MASP-3, a protein with similar domain structure to C1s t

184 FLS were the main source of MASP-1/3 mRNA and protein.

185 we characterize the substrate specificity of MASP-3 by screening against a combinatorial peptide subs

186 The autoactivation steps of MASP-1 were separately quantified using these mutants an

187 e first Michaelis-like complex structures of MASP-1 and MASP-2 formed with substrate-like inhibitors.

188 ASP-1 is about 140-fold faster than those of MASP-2.

189 providing a scenario for transactivation of MASP-2.

190 g does not directly escort the transition of MASP from zymogen to active enzyme in the PRM/MASP compl

191 Autoactivation of MASPs occurs in two steps: 1) zymogen autoactivation, wh

192 A common feature of MASPs is the presence of two conserved regions: an N-ter

193 We decided to clarify the involvement of MASPs in pro-FD activation in normal, as opposed to defi

194 The AP in mice is dependent on MASP-1/3 cleavage of pro-factor D (pro-FD) into mature f

195 serum, MASP-2 activation strictly depends on MASP-1.

196 recombinant MASPs were added to plasma, only MASP-3 could reduce the half-life of pro-FD.

197 -), or MBL-C(-/-) sera; however, MBL-null or MASP-1/-3 KO mouse sera demonstrated significantly decre

198 , the MASP-2 inhibitor, which is also a poor MASP-3 inhibitor, slowed down the activation.

199 fective meniscus-assisted solution printing (MASP) strategy to yield large-grained dense perovskite f

200 mplex activation occurs between discrete PRM/MASP complexes.

201 PRM/MASP complex; rather, clustering of PRM/MASP complexes directly causes activation.

202 ASP from zymogen to active enzyme in the PRM/MASP complex; rather, clustering of PRM/MASP complexes d

203 Proenzyme MASP-1 R448Q readily cleaves synthetic substrates, and i

204 Moreover, both activated and proenzyme MASP-1 can effectively cleave proenzyme MASP-2.

205 zyme MASP-1 can effectively cleave proenzyme MASP-2.

206 ructure of the catalytic region of proenzyme MASP-1 R448Q was solved at 2.5 A.

207 nts, we demonstrated that a stable proenzyme MASP-1 variant (R448Q) cleaved the inactive, catalytic s

208 ectin complement pathway-associated protease MASP-2 to trigger complement deposition.

209 in (MAP) and MBL associated serine protease (MASP) are scarcely investigated.

210 or near the MBL-associated serine protease (MASP) binding site in the collagen stalks of MBL and L-f

211 aces MBL/ficolin-associated serine protease (MASP)-1, MASP-2, and MASP-3 from the MBL complex.

212 BL)-null and MBL-associated serine protease (MASP)-1/-3 knockout (KO) mice had significantly decrease

213 e-binding lectin-associated serine protease (MASP)-1/3(-/-) mice contains pro-FD and has markedly red

214 e-binding lectin-associated serine protease (MASP)-2 has been considered the autonomous initiator of

215 complex with MBL-associated serine protease (MASP)-2, followed by MASP-2 autoactivation and cleavage

216 tor complex, MBL-associated serine protease (MASP)-3/collectin-L1/K1 hetero-oligomer, which impacts c

217 e lectin complement pathway serine proteases MASP-1 and MASP-2.

218 in complex with associated serine proteases MASP-1, -2, and -3 and the non-enzymatic small MBL assoc

219 ed with the MBL-associated serine proteases (MASP)-1 and MASP-2 cleave C4 and C2 to generate C3 conve

220 plexes with MBL-associated serine proteases (MASP-1, -2, and -3) and MBL-associated proteins (MAp19 a

221 f so-called MBL-associated serine proteases (MASP-1, MASP-2, and MASP-3).

222 ns, MBP and MBP-associated serine proteases (MASPs) can replace antibodies and complement components

223 in/collectin-11-associated serine proteases (MASPs) in binding to MBL and the ficolins.

224 Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeos

225 plexed with MBL-associated serine proteases (MASPs) to N. gonorrhoeae was achieved at a concentration

226 -binding lectin-associated serine proteases (MASPs) with affinities in the nM range in vitro and was

227 omplex with MBP-associated serine proteases (MASPs), which become activated upon engagement of a targ

228 -binding lectin-associated serine proteases (MASPs).

229 -binding lectin-associated serine proteases (MASPs).

230 ng lectin (MBL)-associated serine proteases, MASP-1 and MASP-2, have been thought to autoactivate whe

231 copies) of mucin-associated surface protein (MASP) genes.

232 luding the MASP multigene family of proteins MASPs are specific to this parasite and characterized by

233 of MASP activation by MBP, the cDNAs of rat MASP-1 and -2 have been isolated, and portions encompass

234 When recombinant MASPs were added to plasma, only MASP-3 could reduce the

235 s demonstrated in vitro and shown to require MASP-2, C2, and MASP-1/3.

236 The 1.28 A resolution MASP-2 structure reveals significant plasticity of the p

237 This robust MASP strategy may in principle be easily extended to cra

238 Our previously developed selective MASP-1 and MASP-2 inhibitors did not reduce pro-FD activ

239 In normal human serum, MASP-2 activation strictly depends on MASP-1.

240 oligomeric forms of MBL carry only a single MASP homodimer.

241 te that MBL/MASP complexes, and specifically MASP-1, play a key role in thrombus formation in vitro a

242 udy were to determine the cells synthesizing MASP-1/3 and pro-FD in synovial tissue.

243 Hence, in functional terms, it appears that MASP-1 and MASP-2 act in a manner analogous to that of C

244 We further demonstrate that MASP-1 and MASP-2 can associate in the same MBL complex,

245 Furthermore we demonstrated that MASP-1 produces 60% of C2a responsible for C3 convertase

246 inhibitor does the same, demonstrating that MASP-1 is not an auxiliary but an essential pathway comp

247 In summary, our observations emphasize that MASP-3 acts as an important maturase in the AP of comple

248 FD (pro-FD), and it is becoming evident that MASP-3 is implicated in pro-FD maturation.

249 bradykinin; therefore, we hypothesized that MASP-1 levels and the quantity of MASP-1/C1-INH complexe

250 In conclusion, we show that MASP-1/C1-INH complexes circulate in normal human blood.

251 These results suggest that MASP-1 may exert a previously unrecognized role in the p

252 It was suggested that MASP-1 and MASP-3 directly activate pro-FD; however, oth

253 Altogether, these findings suggest that MASPs can associate in various combinations and bring ne

254 The MASP multigene family is specific to T. cruzi, accountin

255 accordance with the key role of MASP-2, the MASP-2 inhibitor completely blocks the lectin pathway ac

256 e presence of an immune response against the MASP C-term region.

257 Moreover, purified EVs as well as the MASP SP inhibit the action of the complement system and

258 In contrast, at very high concentration, the MASP-2 inhibitor, which is also a poor MASP-3 inhibitor,

259 tified immature MASP proteins containing the MASP SP in EVs secreted by the infective forms of the pa

260 Importantly, the MASP-1 inhibitor does the same, demonstrating that MASP-

261 with different protein cargoes including the MASP multigene family of proteins MASPs are specific to

262 -1 also enables modeling and assembly of the MASP-1 molecule in its entirety.

263 The crystal structure of the MASP-2 CUB1-EGF-CUB2 dimer reveals an elongated structur

264 This recognition causes activation of the MASP-2 or the C1s serine proteases followed by cleavage

265 in which the position and orientation of the MASP-binding sites have been changed.

266 phenotype was preserved, indicating that the MASP-2-mediated damage was independent of C4 activation.

267 thway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation

268 When H-ficolin binds to microorganisms the MASPs are activated, which in turn activate the compleme

269 involved in heterocomplex formation with the MASPs thereby breaking the stoichiometry of the activati

270 we found that MAP-1 competes with all three MASPs for ligand binding and is able to mediate a strong

271 ury and indicates that injury occurs through MASP-2-dependent activation events independent of C4.

272 Following cleavage of C4, C4b still binds to MASP-2 (KD approximately 0.6 microM) and dissociates rel

273 When C4 binds to MASP-2, substantial conformational changes in C4 are ind

274 activation via its ability to recruit MBL to MASP, and other hand as a modulator of immune cell activ

275 transmits conformational changes from MBP to MASP that allow activation of its protease activity.

276 MASP-1 transactivates MASP-2 and, although MASP-1 also cleaves C2, MASP-2 clea

277 ncy indicates that binding to both truncated MASP-1 and MASP-2 proteins is defective in such mutants.

278 ified proteins indicates that each truncated MASP is a Ca(2+)-independent homodimer in solution, in w

279 The biophysical properties of the truncated MASPs indicate that the interactions with MBP leading to

280 C patient carrying a previously unidentified MASP-3 G665S mutation prompted us to develop an analytic

281 Using MASP-3-depleted human serum, serum from 3MC patients, an

282 enzymes to be efficient activators, whereas MASP proenzymes lacked such activity.

283 for disease induction, to determine whether MASP-1/3 are required in vivo for the development of tis

284 lels that of the classical pathway, in which MASP-1 and MASP-2 are found together in the same MBL or

285 d as the autonomous pathway-activator, while MASP-1 is considered as an auxiliary component.

286 We found that MAp44 competed with MASP-3 for pattern recognition molecule interaction, and

287 ent activity is introduced concurrently with MASP binding in SP-A but is uncontrolled and occurs even

288 in, as shown by competition experiments with MASP-3.

289 nal failure was no greater than in mice with MASP-2 deficiency alone.

290 ly, and is unaffected by reconstitution with MASP-1 and MASP-3.

291 eric complexes with CL-L1 that interact with MASPs and can mediate complement activation.

292 mplexes, and in the proenzymic phase zymogen MASP-1 controls the process.

293 ainst active MASP-1, indicating that zymogen MASP-1 fluctuates between an inactive and an active-like