Academic Journal
Partial reconstitution of the prophenoloxidase activation system in Anopheles gambiae.
| Τίτλος: | Partial reconstitution of the prophenoloxidase activation system in Anopheles gambiae. |
|---|---|
| Συγγραφείς: | Hou C; Department of Entomology and Plant Pathology, Oklahoma State University, Stillwater, OK 74078., Wang Y; Department of Entomology and Plant Pathology, Oklahoma State University, Stillwater, OK 74078., Jiang H; Department of Entomology and Plant Pathology, Oklahoma State University, Stillwater, OK 74078. |
| Πηγή: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2026 Jun 09; Vol. 123 (23), pp. e2607910123. Date of Electronic Publication: 2026 Jun 03. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : National Academy of Sciences |
| Ιατρικοί όροι (MeSH): | Anopheles*/enzymology , Anopheles*/genetics , Anopheles*/metabolism , Anopheles*/immunology , Enzyme Precursors*/metabolism , Enzyme Precursors*/genetics , Catechol Oxidase*/metabolism , Catechol Oxidase*/genetics , Insect Proteins*/metabolism , Insect Proteins*/genetics, Serine Proteases/metabolism ; Serine Proteases/genetics ; Melanins/metabolism ; Animals ; Melanogenesis ; Enzyme Activation |
| Περίληψη: | Melanization is a central insect immune response to wounding and microbial invasion. It is mediated by a system of serine proteases and their homologs, mostly members of the CLIP subfamily, and leads to prophenoloxidase (proPO) activation and PO-mediated production of cytotoxic compounds and melanin polymers that kill and sequester invading pathogens. In mosquitoes, melanotic encapsulation provides an effective defense against malaria parasites, yet the composition and organization of the underlying serine protease system remain largely unclear. Guided by gene orthology and protein abundance, we expressed SP217, four CLIPCs, and 12 CLIPBs from Anopheles gambiae and reconstructed a five-step branched cascade using purified zymogens. SP217, an ortholog of Drosophila ModSP, initiates the cascade by activating proCLIPC1. CLIPC1 activates proCLIPB13 and proCLIPB47, two of the 10 orthologs of Drosophila Grass and Manduca HP5. CLIPB13 activates proCLIPC4, proCLIPC6, and proCLIPB10 whereas CLIPB47 activates proCLIPC6 only. In the next step, CLIPC6 activates proCLIPB4 and proCLIPB9. CLIPB9 and CLIPB10 function as proPO-activating proteases (PAPs), cleaving proPO2 to generate highly active PO2 in the presence of a cofactor. Together, these results have revealed a framework of the mosquito serine protease system that drives melanization. Our findings highlight both strong evolutionary conservation of the system among holometabolous insects and species-specific differences in its organization, providing a foundation for future analysis through combinational genetic perturbation. |
| Competing Interests: | Competing interests statement:The authors declare no competing interest. |
| References: | Front Immunol. 2023 Sep 15;14:1244792. (PMID: 37781370) PLoS Pathog. 2019 Nov 25;15(11):e1008194. (PMID: 31765430) Biochemistry. 2017 Feb 21;56(7):907-918. (PMID: 28072517) J Innate Immun. 2023;15(1):680-696. (PMID: 37703846) Sci Adv. 2023 Dec 22;9(51):eadk2756. (PMID: 38117884) Immunity. 2010 Jan 29;32(1):41-53. (PMID: 20152169) PLoS Pathog. 2020 Oct 12;16(10):e1008985. (PMID: 33045027) Insect Biochem Mol Biol. 2024 Jan;164:104048. (PMID: 38056530) Cell Microbiol. 2006 Sep;8(9):1392-405. (PMID: 16922859) Cell Mol Life Sci. 2011 Jun;68(11):1929-39. (PMID: 20953892) Insect Biochem Mol Biol. 2016 Apr;71:106-15. (PMID: 26926112) Science. 2002 Oct 4;298(5591):159-65. (PMID: 12364793) Science. 1986 Oct 31;234(4776):607-10. (PMID: 3532325) Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16858-63. (PMID: 17065316) Mol Cell Proteomics. 2002 Apr;1(4):304-13. (PMID: 12096112) J Biol Chem. 2009 Jul 17;284(29):19716-26. (PMID: 19487692) Proc Natl Acad Sci U S A. 2020 Sep 22;117(38):23581-23587. (PMID: 32900946) Curr Opin Insect Sci. 2015 Oct 1;11:47-55. (PMID: 26688791) Microbes Infect. 2024 Jan-Feb;26(1-2):105245. (PMID: 37918462) Proc Natl Acad Sci U S A. 2025 May 6;122(18):e2425863122. (PMID: 40305045) Parasit Vectors. 2018 Sep 27;11(1):528. (PMID: 30261926) Front Cell Infect Microbiol. 2024 Aug 01;14:1438019. (PMID: 39149419) Insect Biochem Mol Biol. 2018 Dec;103:53-69. (PMID: 30367934) J Innate Immun. 2014;6(6):806-18. (PMID: 25012124) Biochimie. 2016 Mar;122:255-69. (PMID: 26453810) Dev Comp Immunol. 2017 Sep;74:110-124. (PMID: 28431895) Insect Biochem Mol Biol. 2017 Sep;88:48-62. (PMID: 28780069) Insect Biochem Mol Biol. 2020 Jan;116:103261. (PMID: 31698082) Front Cell Infect Microbiol. 2021 Jan 15;10:585986. (PMID: 33520733) Trends Parasitol. 2007 Jul;23(7):297-9. (PMID: 17512801) Insect Biochem Mol Biol. 2022 May;144:103762. (PMID: 35395380) Insect Biochem Mol Biol. 2007 Oct;37(10):1015-25. (PMID: 17785189) Insect Biochem Mol Biol. 2025 Feb;177:104254. (PMID: 39799989) J Innate Immun. 2023;15(1):317-332. (PMID: 36423593) Microorganisms. 2024 Mar 12;12(3):. (PMID: 38543619) Science. 2013 May 24;340(6135):984-7. (PMID: 23661646) Insect Biochem Mol Biol. 2006 Sep;36(9):701-11. (PMID: 16935219) J Biol Chem. 2017 Nov 3;292(44):18217-18226. (PMID: 28928218) Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):E1957-62. (PMID: 22623529) Mol Cell Proteomics. 2016 Apr;15(4):1176-87. (PMID: 26811355) |
| Grant Information: | R01 GM058634 United States GM NIGMS NIH HHS; R21 AI180325 United States AI NIAID NIH HHS; GM58634 HHS | NIH | National Institute of General Medical Sciences (NIGMS); AI180325 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) |
| Contributed Indexing: | Keywords: clip domain; insect immunity; melanization; serine protease cascade; zymogen activation |
| Substance Nomenclature: | 0 (Enzyme Precursors) EC 1.10.3.- (pro-phenoloxidase) EC 1.10.3.1 (Catechol Oxidase) 0 (Insect Proteins) EC 3.4.- (Serine Proteases) 0 (Melanins) |
| Entry Date(s): | Date Created: 20260603 Date Completed: 20260606 Latest Revision: 20260813 |
| Update Code: | 20260813 |
| PubMed Central ID: | PMC13240659 |
| DOI: | 10.1073/pnas.2607910123 |
| PMID: | 42234529 |
| Βάση Δεδομένων: | MEDLINE |
καταχωρήστε σχόλιο πρώτοι!