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The structure and function of thioester-containing proteins in arthropods

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Abstract

Thioester-containing proteins (TEPs) form an ancient and diverse family of secreted proteins that play central roles in the innate immune response. Two families of TEPs, complement factors and α2-macroglobulins, have been known and studied in vertebrates for many years, but only in the last decade have crystal structures become available. In the same period, the presence of two additional classes of TEPs has been revealed in arthropods. In this review, we discuss the common structural features TEPs and how this knowledge can be applied to the many arthropod TEPs of unknown function. TEPs perform a wide variety of functions that are driven by different quaternary structures and protein–protein interactions between a common set of folded domains. A common theme is regulated conformational change triggered by proteolysis. Structure-function analysis of the diverse arthropod TEPs may identify not just new mechanisms in innate immunity but also interfaces between immunity, development and cell death.

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References

  • Armstrong PB (2006) Proteases and protease inhibitors: a balance of activities in host-pathogen interaction. Immunobiology 211(4):263–281. doi:10.1016/j.imbio.2006.01.002

    CAS  PubMed  Google Scholar 

  • Armstrong PB, Quigley JP (1987) Limulus a2-macroglobulin. First evidence in an invertebrate for a protein containing an internal thiol ester bond. Biochem J 248(3):703–707

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bányai L, Patthy L (1999) The NTR module: domains of netrins, secreted frizzled related proteins, and type I procollagen C-proteinase enhancer protein are homologous with tissue inhibitors of metalloproteases. Protein Sci 8(8):1636–1642. doi:10.1110/ps.8.8.1636

    PubMed Central  PubMed  Google Scholar 

  • Barrett AJ, Starkey PM (1973) The interaction of alpha 2-macroglobulin with proteinases. Characteristics and specificity of the reaction, and a hypothesis concerning its molecular mechanism. Biochem J 133(4):709–724

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bätz T, Forster D, Luschnig S (2014) The transmembrane protein Macroglobulin complement-related is essential for septate junction formation and epithelial barrier function in Drosophila. Development 141(4):899–908. doi:10.1242/dev.102160

    PubMed  Google Scholar 

  • Baxter RHG, Chang C-I, Chelliah Y, Blandin S, Levashina EA, Deisenhofer J (2007) Structural basis for conserved complement factor-like function in the antimalarial protein TEP1. Proc Natl Acad Sci USA 104(28):11615–11620

    CAS  PubMed Central  PubMed  Google Scholar 

  • Baxter RHG, Steinert S, Chelliah Y, Volohonsky G, Levashina EA, Deisenhofer J (2010) A heterodimeric complex of the LRR proteins LRIM1 and APL1C regulates complement-like immunity in Anopheles gambiae. Proc Natl Acad Sci USA 107(39):16817–16822. doi:10.1073/pnas.1010575107

    CAS  PubMed Central  PubMed  Google Scholar 

  • Blandin S, Levashina EA (2004) Thioester-containing proteins and insect immunity. Mol Immunol 40(12):903–908. doi:10.1016/j.molimm.2003.10.010

    CAS  PubMed  Google Scholar 

  • Blandin S, Shiao S-H, Moita LF, Janse CJ, Waters AP, Kafatos FC, Levashina EA (2004) Complement-like protein TEP1 is a determinant of vectorial capacity in the malaria vector Anopheles gambiae. Cell 116(5):661–670. doi:10.1016/S0092-8674(04)00173-4

    CAS  PubMed  Google Scholar 

  • Blandin SA, Wang-Sattler R, Lamacchia M, Gagneur J, Lycett G, Ning Y, Levashina EA, Steinmetz LM (2009) Dissecting the genetic basis of resistance to malaria parasites in Anopheles gambiae. Science 326(5949):147–150. doi:10.1126/science.1175241

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bork P, Beckmann G (1993) The CUB domain. A widespread module in developmentally regulated proteins. J Mol Biol 231(2):539–545. doi:10.1006/jmbi.1993.1305

    CAS  PubMed  Google Scholar 

  • Bou Aoun R, Hetru C, Troxler L, Doucet D, Ferrandon D, Matt N (2011) Analysis of thioester-containing proteins during the innate immune response of Drosophila melanogaster. J Innate Immun 3(1):52–64. doi:10.1159/000321554

    CAS  PubMed  Google Scholar 

  • Buresova V, Hajdusek O, Franta Z, Sojka D, Kopacek P (2009) IrAM-An a2-macroglobulin from the hard tick Ixodes ricinus: characterization and function in phagocytosis of a potential pathogen Chryseobacterium indologenes. Dev Comp Immunol 33(4):489–498. doi:10.1016/j.dci.2008.09.011

    CAS  PubMed  Google Scholar 

  • Buresova V, Hajdusek O, Franta Z, Loosova G, Grunclova L, Levashina EA, Kopacek P (2011) Functional genomics of tick thioester-containing proteins reveal the ancient origin of the complement system. J Innate Immun 3(6):623–630. doi:10.1159/000328851

    CAS  PubMed  Google Scholar 

  • Cheng G, Liu L, Wang P, Zhang Y, Zhao YO, Colpitts TM, Feitosa F, Anderson JF, Fikrig E (2011) An in vivo transfection approach elucidates a role for Aedes aegypti thioester-containing proteins in flaviviral infection. PLoS ONE 6(7):e22786. doi:10.1371/journal.pone.0022786

    CAS  PubMed Central  PubMed  Google Scholar 

  • Christophides GK, Zdobnov E, Barillas-Mury C, Birney E, Blandin S, Blass C, Brey PT, Collins FH, Danielli A, Dimopoulos G, Hetru C, Hoa NT, Hoffmann JA, Kanzok SM, Letunic I, Levashina EA, Loukeris TG, Lycett G, Meister S, Michel K, Moita LF, Muller H-M, Osta MA, Paskewitz SM, Reichhart J-M et al (2002) Immunity-related genes and gene families in Anopheles gambiae. Science 298(5591):159–165. doi:10.1126/science.1077136

    CAS  PubMed  Google Scholar 

  • Chu CT, Howard GC, Misra UK, Pizzo SV (1994) a2-macroglobulin: a sensor for proteolysis. Ann NY Acad Sci 737:291–307

    CAS  PubMed  Google Scholar 

  • Crews BC, James MW, Beth AH, Gettins P, Cunningham LW (1987) In support of the trap hypothesis. Chymotrypsin is not rigidly held in its complex with human a2-macroglobulin. Biochemistry 26(19):5963–5967

    CAS  PubMed  Google Scholar 

  • Day NK, Gewurz H, Johannsen R, Finstad J, Good RA (1970) Complement and complement-like activity in lower vertebrates and invertebrates. J Exp Med 132(5):941–950

    CAS  PubMed Central  PubMed  Google Scholar 

  • Doan N, Gettins PGW (2007) Human a2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3. Biochem J 407(1):23–30. doi:10.1042/BJ20070764

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dodds AW, Law SKA (1988) Structural basis of the binding specificity of the thioester-containing proteins, C4, C3 and a2-macroglobulin. Complement 5(2):89–97

    CAS  PubMed  Google Scholar 

  • Dodds AW, Law SKA (1990) The complement component C4 of mammals. Biochem J 265(2):495–502

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dodds AW, Ren X-D, Willis AC, Law SK (1996) The reaction mechanism of the internal thioester in the human complement component C4. Nature 379(6561):177–179. doi:10.1038/379177a0

    CAS  PubMed  Google Scholar 

  • Edgecombe GD (2010) Arthropod phylogeny: an overview from the perspectives of morphology, molecular data and the fossil record. Arthropod Struct Dev 39(2–3):74–87. doi:10.1016/j.asd.2009.10.002

    PubMed  Google Scholar 

  • Erler S, Popp M, Lattorff HMG (2011) Dynamics of immune system gene expression upon bacterial challenge and wounding in a social insect (Bombus terrestris). PLoS ONE 6(3):e18126. doi:10.1371/journal.pone.0018126

    CAS  PubMed Central  PubMed  Google Scholar 

  • Feldman SR, Gonias SL, Pizzo SV (1985) Model of a2-macroglobulin structure and function. Proc Natl Acad Sci USA 82(17):5700–5704

    CAS  PubMed Central  PubMed  Google Scholar 

  • Forneris F, Ricklin D, Wu J, Tzekou A, Wallace RS, Lambris JD, Gros P (2010) Structures of C3b in complex with factors B and D give insight into complement convertase formation. Science 330(6012):1816–1820. doi:10.1126/science.1195821

    CAS  PubMed Central  PubMed  Google Scholar 

  • Forneris F, Wu J, Gros P (2012) The modular serine proteases of the complement cascade. Curr Opin Struct Biol 22(3):333–341. doi:10.1016/j.sbi.2012.04.001

    CAS  PubMed  Google Scholar 

  • Fraiture M, Baxter RHG, Steinert S, Chelliah Y, Frolet C, Quispe-Tintaya W, Hoffmann JA, Blandin S, Levashina EA (2009) Two mosquito LRR proteins function as complement control factors in the TEP1-mediated killing of Plasmodium. Cell Host Microbe 5(3):273–284. doi:10.1016/j.chom.2009.01.005

    CAS  PubMed  Google Scholar 

  • Fredslund F, Jenner L, Husted LB, Nyborg J, Andersen GR, Sottrup-Jensen L (2006) The structure of bovine complement component 3 reveals the basis for thioester function. J Mol Biol 361(1):115–127

    CAS  PubMed  Google Scholar 

  • Fredslund F, Laursen NS, Roversi P, Jenner L, Oliveira CL, Pedersen JS, Nunn MA, Lea SM, Discipio R, Sottrup-Jensen L, Andersen GR (2008) Structure of and influence of a tick complement inhibitor on human complement component 5. Nat Immunol 9(7):753–760

    CAS  PubMed  Google Scholar 

  • Garcia BL, Ramyar KX, Tzekou A, Ricklin D, McWhorter WJ, Lambris JD, Geisbrecht BV (2010) Molecular basis for complement recognition and inhibition determined by crystallographic studies of the staphylococcal complement inhibitor (SCIN) bound to C3c and C3b. J Mol Biol 402(1):17–29. doi:10.1016/j.jmb.2010.07.029

    CAS  PubMed Central  PubMed  Google Scholar 

  • Grimaldi DA (2010a) 400 million years on six legs: on the origin and early evolution of Hexapoda. Arthropod Struct Dev 39(2–3):191–203. doi:10.1016/j.asd.2009.10.008

    PubMed  Google Scholar 

  • Grimaldi DA (2010b) Fossil record and phylogeny of the Arthropoda: introduction. Arthropod Struct Dev 39(2–3):72–73. doi:10.1016/j.asd.2010.01.001

    PubMed  Google Scholar 

  • Gros P, Milder FJ, Janssen BJC (2008) Complement driven by conformational changes. Nat Rev Immunol 8(1):48–58. doi:10.1038/nri2231

    CAS  PubMed  Google Scholar 

  • Gunaratna RT, Jiang H (2013) A comprehensive analysis of the Manduca sexta immunotranscriptome. Dev Comp Immunol 39(4):388–398. doi:10.1016/j.dci.2012.10.004

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hadders MA, Bubeck D, Roversi P, Hakobyan S, Forneris F, Morgan BP, Pangburn MK, Llorca O, Lea SM, Gros P (2012) Assembly and regulation of the membrane attack complex based on structures of C5b6 and sC5b9. Cell Rep 1(3):200–207

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hall S, Bone C, Oshima K, Zhang L, McGraw M, Lucas B, Fehon RG, Ward RE (2014) Macroglobulin complement-related encodes a protein required for septate junction organization and paracellular barrier function in Drosophila. Development 141(4):889–898. doi:10.1242/dev.102152

    CAS  PubMed  Google Scholar 

  • Isenman DE, Kells DIC, Cooper NR, Müller-Eberhard HJ, Pangburn MK (1981) Nucleophilic modification of human complement protein C3: correlation of conformational changes with acquisition of C3b-like functional properties. Biochemistry 20(15):4458–4467

    CAS  PubMed  Google Scholar 

  • Ishii N, Wadsworth WG, Stern BD, Culotti JG, Hedgecock EM (1992) UNC-6, a laminin-related protein, guides cell and pioneer axon migrations in C. elegans. Neuron 9(5):873–881

    CAS  PubMed  Google Scholar 

  • Jacob F (1977) Evolution and tinkering. Science 196(4295):1161–1166

    CAS  PubMed  Google Scholar 

  • Janatova J, Lorenz PE, Schechter AN, Prahl JW, Tack BF (1980) Third component of human complement: appearance of a sulfhydryl group following chemical or enzymatic inactivation. Biochemistry 19(19):4471–4478

    CAS  PubMed  Google Scholar 

  • Jang I-H, Nam H-J, Lee W-J (2008) CLIP-domain serine proteases in Drosophila innate immunity. BMB Rep 41(2):102–107

    CAS  PubMed  Google Scholar 

  • Janssen BJC, Huizinga EG, Raaijmakers HCA, Roos A, Daha MR, Nilsson-Ekdahl K, Nilsson B, Gros P (2005) Structures of complement component C3 provide insights into the function and evolution of immunity. Nature 437(7058):505–511. doi:10.1038/nature04005

    CAS  PubMed  Google Scholar 

  • Janssen BJC, Christodoulidou A, McCarthy A, Lambris JD, Gros P (2006) Structure of C3b reveals conformational changes that underlie complement activity. Nature 444(7116):213–216. doi:10.1038/nature05172

    CAS  PubMed  Google Scholar 

  • Janssen BJC, Gomes L, Koning RI, Svergun DI, Koster AJ, Fritzinger DC, Vogel C-W, Gros P (2009) Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex. EMBO J 28(16):2469–2478. doi:10.1038/emboj.2009.184

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jenkins VK, Timmons AK, McCall K (2013) Diversity of cell death pathways: insight from the fly ovary. Trends Cell Biol 23(11):567–574. doi:10.1016/j.tcb.2013.07.005

    CAS  PubMed  Google Scholar 

  • Jenner L, Husted LB, Thirup S, Sottrup-Jensen L, Nyborg J (1998) Crystal structure of the receptor-binding domain of a2-macroglobulin. Structure 6(5):595–604

    CAS  PubMed  Google Scholar 

  • Jensen JA, Festa E, Smith DS, Cayer M (1981) The complement system of the nurse shark: hemolytic and comparative characteristics. Science 214(4520):566–569

    CAS  PubMed  Google Scholar 

  • Jiang H, Kanost MR (2000) The clip-domain family of serine proteinases in arthropods. Insect Biochem Mol Biol 30(2):95–105

    CAS  PubMed  Google Scholar 

  • Jiang H, Vilcinskas A, Kanost MR (2010) Immunity in lepidopteran insects. Adv Exp Med Biol 708:181–204

    CAS  PubMed  Google Scholar 

  • Khan SA, Erickson BW (1982) An equilibrium model of the metastable binding sites of a2-macroglobulin and complement proteins C3 and C4. J Biol Chem 257(20):11864–11867

    CAS  PubMed  Google Scholar 

  • Khan SA, Erickson BW (1981) Synthesis of macrocyclic peptide thiolactones as models of the metastable binding-sites of alpha-2-macroglobulin and complement protein C3b. J Am Chem Soc 103(24):7374–7376. doi:10.1021/Ja00414a075

    CAS  Google Scholar 

  • Khan SA, Sekulski JM, Erickson BW (1986) Peptide models of protein metastable binding sites: competitive kinetics of isomerization and hydrolysis. Biochemistry 25(18):5165–5171

    CAS  PubMed  Google Scholar 

  • Kidmose RT, Laursen NS, Dobo J, Kjaer TR, Sirotkina S, Yatime L, Sottrup-Jensen L, Thiel S, Gal P, Andersen GR (2012) Structural basis for activation of the complement system by component C4 cleavage. Proc Natl Acad Sci USA 109(38):15425–15430. doi:10.1073/pnas.1208031109

    CAS  PubMed Central  PubMed  Google Scholar 

  • Klos A, Wende E, Wareham KJ, Monk PN (2013) International Union of Pharmacology. LXXXVII. Complement peptide C5a, C4a, and C3a receptors. Pharmacol Rev 65(1):500–543

    PubMed  Google Scholar 

  • Kopacek P, Weise C, Saravanan T, Vitova K, Grubhoffer L (2000) Characterization of an a-macroglobulin-like glycoprotein isolated from the plasma of the soft tick Ornithodoros moubata. Eur J Biochem 267(2):465–475

    CAS  PubMed  Google Scholar 

  • Kopacek P, Hajdusek O, Buresova V (2012) Tick as a model for the study of a primitive complement system. Adv Exp Med Biol 710:83–93. doi:10.1007/978-1-4419-5638-5_9

    CAS  PubMed  Google Scholar 

  • Krishnan V, Ponnuraj K, Xu Y, Macon K, Volanakis JE, Narayana SVL (2009) The crystal structure of cobra venom factor, a cofactor for C3- and C5-convertase CVFBb. Structure 17(4):611–619. doi:10.1016/j.str.2009.01.015

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lagueux M, Perrodou E, Levashina EA, Capovilla M, Hoffmann JA (2000) Constitutive expression of a complement-like protein in toll and JAK gain-of-function mutants of Drosophila. Proc Natl Acad Sci USA 97(21):11427–11432. doi:10.1073/pnas.97.21.11427

    CAS  PubMed Central  PubMed  Google Scholar 

  • Laursen NS, Gordon N, Hermans S, Lorenz N, Jackson N, Wines B, Spillner E, Christensen JB, Jensen M, Fredslund F, Bjerre M, Sottrup-Jensen L, Fraser JD, Andersen GR (2010) Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus. Proc Natl Acad Sci USA 107(8):3681–3686. doi:10.1073/pnas.0910565107

    CAS  PubMed Central  PubMed  Google Scholar 

  • Law SK, Dodds AW (1997) The internal thioester and the covalent binding properties of the complement proteins C3 and C4. Protein Sci 6(2):263–274. doi:10.1002/pro.5560060201

    CAS  PubMed Central  PubMed  Google Scholar 

  • Law SK, Lichtenberg NA, Levine RP (1980) Covalent binding and hemolytic activity of complement proteins. Proc Natl Acad Sci U S A 77(12):7194–7198

    CAS  PubMed Central  PubMed  Google Scholar 

  • Law SKA, Dodds AW, Porter RR (1984) A comparison of the properties of two classes, C4A and C4B, of the human complement component C4. EMBO J 3(8):1819–1823

    CAS  PubMed Central  PubMed  Google Scholar 

  • Le BV, Williams M, Logarajah S, Baxter RHG (2012) Molecular basis for genetic resistance of Anopheles gambiae to Plasmodium: structural analysis of TEP1 susceptible and resistant alleles. PLoS Pathog 8(10):e1002958. doi:10.1371/journal.ppat.1002958

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lea SM, Johnson S (2012) Putting the structure into complement. Immunobiology 217(11):1117–1121. doi:10.1016/j.imbio.2012.07.005

    CAS  PubMed Central  PubMed  Google Scholar 

  • Leahy DJ, Hendrickson WA, Aukhil I, Erickson HP (1992) Structure of a fibronectin type III domain from tenascin phased by MAD analysis of the selenomethionyl protein. Science 258(5084):987–991

    CAS  PubMed  Google Scholar 

  • Levashina EA, Moita LF, Blandin S, Vriend G, Lagueux M, Kafatos FC (2001) Conserved role of a complement-like protein in phagocytosis revealed by dsRNA knockout in cultured cells of the mosquito, Anopheles gambiae. Cell 104(5):709–718

    CAS  PubMed  Google Scholar 

  • Liszewski MK, Kolev M, Le Friec G, Leung M, Bertram PG, Fara AF, Subias M, Pickering MC, Drouet C, Meri S, Arstila TP, Pekkarinen PT, Ma M, Cope A, Reinheckel T, Rodriguez de Cordoba S, Afzali B, Atkinson JP, Kemper C (2013) Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation. Immunity 39(6):1143–1157. doi:10.1016/j.immuni.2013.10.018

    CAS  PubMed Central  PubMed  Google Scholar 

  • Marrero A, Duquerroy S, Trapani S, Goulas T, Guevara T, Andersen GR, Navaza J, Sottrup-Jensen L, Gomis-Rüth FX (2012) The crystal structure of human α2-macroglobulin reveals a unique molecular cage. Angew Chem Int Ed 51(13):3340–3344. doi:10.1002/anie.201108015

    CAS  Google Scholar 

  • Mitri C, Jacques J-C, Thiery I, Riehle MM, Xu J, Bischoff E, Morlais I, Nsango SE, Vernick KD, Bourgouin C (2009) Fine pathogen discrimination within the APL1 gene family protects Anopheles gambiae against human and rodent malaria species. PLoS Pathog 5(9):e1000576. doi:10.1371/journal.ppat.1000576

    PubMed Central  PubMed  Google Scholar 

  • Moita LF, Wang-Sattler R, Michel K, Zimmermann T, Blandin S, Levashina EA, Kafatos FC (2005) In vivo identification of novel regulators and conserved pathways of phagocytosis in A. gambiae. Immunity 23(1):65–73

    CAS  PubMed  Google Scholar 

  • Molina-Cruz A, DeJong RJ, Ortega C, Haile A, Abban E, Rodrigues J, Jaramillo-Gutierrez G, Barillas-Mury C (2012) Some strains of Plasmodium falciparum, a human malaria parasite, evade the complement-like system of Anopheles gambiae mosquitoes. Proc Natl Acad Sci USA 109(28):E1957–1962. doi:10.1073/pnas.1121183109

    CAS  PubMed Central  PubMed  Google Scholar 

  • Molina-Cruz A, Garver LS, Alabaster A, Bangiolo L, Haile A, Winikor J, Ortega C, van Schaijk BCL, Sauerwein RW, Taylor-Salmon E, Barillas-Mury C (2013) The human malaria parasite Pfs47 gene mediates evasion of the mosquito immune system. Science 340(6135):984–987. doi:10.1126/science.1235264

    CAS  PubMed  Google Scholar 

  • Mone Y, Gourbal B, Duval D, Du Pasquier L, Kieffer-Jaquinod S, Mitta G (2010) A large repertoire of parasite epitopes matched by a large repertoire of host immune receptors in an invertebrate host/parasite model. PLoS Negl Trop Dis 4(9):e813. doi:10.1371/journal.pntd.0000813

    PubMed Central  PubMed  Google Scholar 

  • Morikis D, Holland CH, Lambris JD (2005) Structure of the anaphylatoxins C3a and C5a. In: Morikis D, Lambris JD (eds) Structural Biology of the Complement System. CRC, Boca Raton, pp 161–178

  • Mudiganti U, Hernandez R, Brown DT (2010) Insect response to alphavirus infection–establishment of alphavirus persistence in insect cells involves inhibition of viral polyprotein cleavage. Virus Res 150(1–2):73–84. doi:10.1016/j.virusres.2010.02.016

    CAS  PubMed  Google Scholar 

  • Müller-Eberhard HJ (1975) Complement. Annu Rev Biochem 44:697–724. doi:10.1146/annurev.bi.44.070175.003405

    PubMed  Google Scholar 

  • Nagar B, Jones RG, Diefenbach RJ, Isenman DE, Rini JM (1998) X-ray crystal structure of C3d: a C3 fragment and ligand for complement receptor 2. Science 280(5367):1277–1281. doi:10.1126/science.280.5367.1277

    CAS  PubMed  Google Scholar 

  • Neves D, Estrozi LF, Job V, Gabel F, Schoehn G, Dessen A (2012) Conformational states of a bacterial a2-macroglobulin resemble those of human complement C3. PLoS ONE 7(4):e35384. doi:10.1371/journal.pone.0035384

    CAS  PubMed Central  PubMed  Google Scholar 

  • Oliveira GA, Lieberman J, Barillas-Mury C (2012) Epithelial nitration by a peroxidase/NOX5 system mediates mosquito antiplasmodial immunity. Science 335(6070):856–859. doi:10.1126/science.1209678

    CAS  Google Scholar 

  • Osta MA, Christophides GK, Kafatos FC (2004) Effects of mosquito genes on Plasmodium development. Science 303(5666):2030–2032

    CAS  PubMed  Google Scholar 

  • Pangburn MK, Müller-Eberhard HJ (1980) Relation of putative thioester bond in C3 to activation of the alternative pathway and the binding of C3b to biological targets of complement. J Exp Med 152(4):1102–1114

    CAS  PubMed  Google Scholar 

  • Povelones M, Waterhouse RM, Kafatos FC, Christophides GK (2009) Leucine-rich repeat protein complex activates mosquito complement in defense against Plasmodium parasites. Science 324(5924):258–261. doi:10.1126/science.1171400

    CAS  PubMed Central  PubMed  Google Scholar 

  • Povelones M, Upton LM, Sala KA, Christophides GK (2011) Structure-function analysis of the Anopheles gambiae LRIM1/APL1C complex and its interaction with complement C3-like protein TEP1. PLoS Pathog 7(4):e1002023. doi:10.1371/journal.ppat.1002023

    CAS  PubMed Central  PubMed  Google Scholar 

  • Povelones M, Bhagavatula L, Yassine H, Tan LA, Upton LM, Osta MA, Christophides GK (2013) The CLIP-domain serine protease homolog SPCLIP1 regulates complement recruitment to microbial surfaces in the malaria mosquito Anopheles gambiae. PLoS Pathog 9(9):e1003623. doi:10.1371/journal.ppat.1003623

    CAS  PubMed Central  PubMed  Google Scholar 

  • Quigley JP, Armstrong PB (1983) An endopeptidase inhibitor, similar to mammalian a2-macroglobulin, detected in the hemolymph of an invertebrate, Limulus polyphemus. J Biol Chem 258(13):7903–7906

    CAS  PubMed  Google Scholar 

  • Quigley JP, Armstrong PB (1985) A homologue of a2-macroglobulin purified from the hemolymph of the horseshoe crab Limulus polyphemus. J Biol Chem 260(23):12715–12719

    CAS  PubMed  Google Scholar 

  • Rehman AA, Ahsan H, Khan FH (2013) Alpha-2-macroglobulin: a physiological guardian. J Cell Physiol 228(8):1665–1675. doi:10.1002/jcp.24266

    CAS  PubMed  Google Scholar 

  • Ricklin D, Hajishengallis G, Yang K, Lambris JD (2010) Complement: a key system for immune surveillance and homeostasis. Nat Immunol 11(9):785–797. doi:10.1038/ni.1923

    CAS  PubMed Central  PubMed  Google Scholar 

  • Riehle MM, Kyriacos M, Niaré O, Xu J, Li J, Touré AM, Podiougou B, Oduol F, Diawara S, Diallo M, Coulibaly B, Ouatara A, Kruglyak L, Traoré SF, Vernick KD (2006) Natural malaria infection in Anopheles gambiae is regulated by a single genomic control region. Science 312(5773):577–579

    CAS  PubMed  Google Scholar 

  • Romero A, Romao MJ, Varela PF, Kölln I, Dias JM, Carvalho AL, Sanz L, Töpfer-Petersen E, Calvete JJ (1997) The crystal structures of two spermadhesins reveal the CUB domain fold. Nat Struct Biol 4(10):783–788

    CAS  PubMed  Google Scholar 

  • Rooijakkers SH, Wu J, Ruyken M, van Domselaar R, Planken KL, Tzekou A, Ricklin D, Lambris JD, Janssen BJC, van Strijp JAG, Gros P (2009) Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor. Nat Immunol 10(7):721–727

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sepp A, Dodds AW, Anderson M, Campbell RD, Willis AC, Law SKA (1993) Covalent binding properties of the human complement protein C4 and hydrolysis rate of the internal thioester upon activation. Protein Sci 2(5):706–716. doi:10.1002/pro.5560020502

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sim RB, Sim E (1981) Autolytic fragmentation of complement components C3 and C4 under denaturing conditions, a property shared with a2-macroglobulin. Biochem J 193(1):129–141

    CAS  PubMed Central  PubMed  Google Scholar 

  • Starkey PM, Barrett AJ (1982a) Evolution of a2-macroglobulin. The demonstration in a variety of vertebrate species of a protein resembling human a2-macroglobulin. Biochem J 205(1):91–95

    CAS  PubMed Central  PubMed  Google Scholar 

  • Starkey PM, Barrett AJ (1982b) Evolution of a2-macroglobulin. The structure of a protein homologous with human a2-macroglobulin from plaice (Pleuronectes platessa L.) plasma. Biochem J 205(1):105–115

    CAS  PubMed Central  PubMed  Google Scholar 

  • Starkey PM, Fletcher TC, Barrett AJ (1982) Evolution of a2-macroglobulin. The purification and characterization of a protein homologous with human a2-macroglobulin from plaice (Pleuronectes platessa L.) plasma. Biochem J 205(1):97–104

    CAS  PubMed Central  PubMed  Google Scholar 

  • Stroschein-Stevenson SL, Foley E, O’Farrell PH, Johnson AD (2006) Identification of Drosophila gene products required for phagocytosis of Candida albicans. PLoS Biol 4(1):e4. doi:10.1371/journal.pbio.0040004

    PubMed Central  PubMed  Google Scholar 

  • Szakonyi G, Guthridge JM, Li D, Young K, Holers VM, Chen XS (2001) Structure of complement receptor 2 in complex with its C3d ligand. Science 292(5522):1725–1728. doi:10.1126/science.1059118

    CAS  PubMed  Google Scholar 

  • Tack BF, Harrison RA, Janatova J, Thomas ML, Prahl JW (1980) Evidence for presence of an internal thiolester bond in third component of human complement. Proc Natl Acad Sci USA 77(10):5764–5768

    CAS  PubMed Central  PubMed  Google Scholar 

  • van den Elsen JMH, Isenman DE (2011) A crystal structure of the complex between human complement receptor 2 and its ligand C3d. Science 332(6029):608–611. doi:10.1126/science.1201954

    PubMed  Google Scholar 

  • Varela PF, Romero A, Sanz L, Romão MJ, Töpfer-Petersen E, Calvete JJ (1997) The 2.4 a resolution crystal structure of boar seminal plasma PSP-I/PSP-II: a zona pellucida-binding glycoprotein heterodimer of the spermadhesin family built by a CUB domain architecture. J Mol Biol 274(4):635–649. doi:10.1006/jmbi.1997.1424

    CAS  PubMed  Google Scholar 

  • Waterhouse RM, Kriventseva EV, Meister S, Xi Z, Alvarez KS, Bartholomay LC, Barillas-Mury C, Bian G, Blandin S, Christensen BM, Dong Y, Jiang H, Kanost MR, Koutsos AC, Levashina EA, Li J, Ligoxygakis P, Maccallum RM, Mayhew GF, Mendes A, Michel K, Osta MA, Paskewitz S, Shin SW, Vlachou D et al (2007) Evolutionary dynamics of immune-related genes and pathways in disease-vector mosquitoes. Science 316(5832):1738–1743. doi:10.1126/science.1139862

    CAS  PubMed Central  PubMed  Google Scholar 

  • Waterhouse RM, Povelones M, Christophides GK (2010) Sequence-structure-function relations of the mosquito leucine-rich repeat immune proteins. BMC Genomics 11:531. doi:10.1186/1471-2164-11-531

    PubMed Central  PubMed  Google Scholar 

  • Weiss BL, Wang J, Aksoy S (2011) Tsetse immune system maturation requires the presence of obligate symbionts in larvae. PLoS Biol 9(5):e1000619. doi:10.1371/journal.pbio.1000619

    CAS  PubMed Central  PubMed  Google Scholar 

  • White BJ, Lawniczak MKN, Cheng C, Coulibaly MB, Wilson MD, Sagnon NF, Costantini C, Simard F, Christophides GK, Besansky NJ (2011) Adaptive divergence between incipient species of Anopheles gambiae increases resistance to Plasmodium. Proc Natl Acad Sci USA 108(1):244–249. doi:10.1073/pnas.1013648108

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wiesmann C, Katschke KJ, Yin J, Helmy KY, Steffek M, Fairbrother WJ, McCallum SA, Embuscado L, DeForge L, Hass PE, van Lookeren CM (2006) Structure of C3b in complex with CRIg gives insights into regulation of complement activation. Nature 444(7116):217–220

    CAS  PubMed  Google Scholar 

  • Wu J, Wu Y-Q, Ricklin D, Janssen BJC, Lambris JD, Gros P (2009) Structure of complement fragment C3b-factor H and implications for host protection by complement regulators. Nat Immunol 10(7):728–733

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xiao T, DeCamp DL, Sprang SR (2000) Structure of a rat a1-macroglobulin receptor-binding domain dimer. Protein Sci 9(10):1889–1897. doi:10.1110/ps.9.10.1889

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhao P, Dong Z, Duan J, Wang G, Wang L, Li Y, Xiang Z, Xia Q (2012) Genome-wide identification and immune response analysis of serine protease inhibitor genes in the silkworm, Bombyx mori. PLoS ONE 7(2):e31168. doi:10.1371/journal.pone.0031168

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhu Y, Thangamani S, Ho B, Ding JL (2005) The ancient origin of the complement system. EMBO J 24(2):382–394. doi:10.1038/sj.emboj.7600533

    CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

The authors express their thanks to members of the Baxter Laboratory and their collaborators for helpful discussions over the years.

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Marni Williams declares that she has no conflict of interest. Richard Baxter declares that he has no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by the any of the authors.

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Williams, M., Baxter, R. The structure and function of thioester-containing proteins in arthropods. Biophys Rev 6, 261–272 (2014). https://doi.org/10.1007/s12551-014-0142-6

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