烟草天蛾血淋巴中免疫丝氨酸蛋白酶系统的构成及调控

Constitutionandregulationoftheimmuneserineprotease(SP)systeminhemolymphofthetobaccohornworm,Manducata Thetobaccohornworm taLarvaefeedonsolanaceous(茄科 Modelinsectnt-insect Innate阻遏

昆 巴天然免疫系统概应激

?

浆质细作作巴凝酶原巴凝

细胞介素开结瘤反包囊形结瘤反包囊形 合成免疫蛋白，如抗菌MelanizationChemistryofmelanizationandphenoloxidase(PO,苯酚氧化酶)-catalyzedreactions

DDC

NDCEN

OdopamineO H

DHIBroadspectrumantibioticactivityofPO-generatedreactivecompoundsGram+bacteria:B.cereus,B.subtilis,M.luteus,S.Gram-bacteria:E.coli,K. Fungi:P.pastoris,S.cerevisiae,C.albican,B.es:λbacteriophage,Parasitoidwaspeggs:M.Insectcells:S.frugiperdaSf9 … HumanbloodC1

FactorXII

Factor

C1Factor FactorFactor

Factor Factor FactorFactor

FactorXaFactor

FactorinactivatedXa

antithrombin,heparincofactor Protein

XIIIa

ProteinC

fibrinclot tPA,Protein

PAI-

AcofactorneededforproPOactivationby

silkwormPAP1+unknown

pro-region+POpro-region+

PO*

1or

protease-

PO*

SPH:serineproteasehomologPAP:proPOactivatingprotease

2003系统拓

2003cDNAcloningHP1,HP2,HP3,HP5throughSPH1PAP1PAP2? fungalβ1,3-

+

Systemstrengthening系统加强

2010++

++

PGRP1+MBP? ?

PO*

PO*

++

PAP32014+

+

Spn-Spn-

+

AMP

Spn-

proPO +

Spn-1J,3,6, 2014modelwithHP1a-CLIPD90%Encodedby

# I │ Y-separate activationsiteHP1:

DKF F

SS

DI- @ EK NYA-

@ binantproHP1a/bandHP1a/binducesproPOactivationinlarval

6 4

kDaAb:HP6

POPOactivity10543210sma

40840

●■CH

CPC-treatedproHP1cutsproHP6atawrong Ab:

SS

HP6:

proteaseproteaseS►►►►◄◄○○■-■+

CPCinducesLDLHpNahydrolysisbythefour binantproteinsHP6:LDLHaseLDLHaseactivity

SS

S++++++++++++++++++

CPC-treatedproHP1cutsproHP6atawrong Ab:

SS+++++++++++++++++++

HP6:

proteaseprotease►►►►◄◄○○■-■+

CleavageofproHP6byHP1a/bA

Ab:

Ab:

◄ ◄ +

-

■+++++++++++++++++ +++++++++ +++++++ ab IH

Serpinsareafamilyof~45kDaserineproteaseinhibitorsthatformacyl-enzymecomplexwithcognateproteases,onlywhentheactiveSPsareattackingtheserpinsattheirreactivecenterloop.TheloopundergoesamajorconformationalchangethatentrapsandinactivatestheenzymeinanSDS-stablecomplex.Affinity

PFTW1W2E1E2E3E4E5E6E7

PFTW1W2E1E2E3E4E5E6E7ofproHP1andassociated

C150with

D

no

HP1HP1a,HP1b,serpin-1,-3,-4,-5,--9,-13,-15,andtwenty-sixproteinsinthe80−95kDa

HP1

4

HP113

HP1

HP1

E1A 15B Identificationofthreetrypticpeptidesinthe andlinkerregionofproHP1a

S-IntensityIntensity

Retentiontime

MutantHP1bcutatthepredictedactivationsitedoesnotactivateproHP6

PQGRto

FactorXa

ProHP1’sputativeroleinHP6

proHP1+serpin-1,9,13proHP1

?

Currentviewofthe+

+

Serpin-4,

Spn-1, 13,3,

AMP

?GBP,

+

Serpin-1J,3,6,

Activationandfunctionsofputativecytokines:PSP/PP,uENFs,GBP,SRPs,Spätzle-2,-7etc.Possiblerolesoftheother26SPsandSPHsidentifiedinthelarvalhemolymphInhibitoryregulationoftheSPsystembyadditionalOklahomaStateXiaolongCao,YanHe,YingxiaHu,FanYang,XuesongHe,ShuguangZhang,XiufengZhang,PichengZhao,RudanHuang,SiweiLiu,ZhiqiangLu,ChuanyiJi,ZhenZou,YangWang,JunpengDeng,SteveHartson,JanetRogers,KrishnaBhattari,MansiGulati,RameshGunaratna,SubrahmanyamRayaprolu,Niranji