Invariant surface glycoprotein 65 of Trypanosoma brucei is a complement C3 receptor.
| Title: | Invariant surface glycoprotein 65 of Trypanosoma brucei is a complement C3 receptor. |
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| Authors: | Macleod OJS; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.; Cook AD; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.; Webb H; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.; Crow M; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.; Burns R; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.; Redpath M; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.; Seisenberger S; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.; Trevor CE; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.; Peacock L; Bristol Veterinary School and School of Biological Sciences, University of Bristol, Bristol, UK.; Schwede A; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.; Kimblin N; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.; Francisco AF; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.; Pepperl J; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.; Rust S; Antibody Discovery and Protein Engineering, Biopharmaceuticals R&D, AstraZeneca, Cambridge, UK.; Voorheis P; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.; Gibson W; Bristol Veterinary School and School of Biological Sciences, University of Bristol, Bristol, UK.; Taylor MC; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.; Higgins MK; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK. matthew.higgins@bioch.ox.ac.uk.; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK. matthew.higgins@bioch.ox.ac.uk.; Carrington M; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK. mc115@cam.ac.uk. |
| Source: | Nature communications [Nat Commun] 2022 Aug 29; Vol. 13 (1), pp. 5085. Date of Electronic Publication: 2022 Aug 29. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| MeSH Terms: | Trypanosoma*/physiology ; Trypanosoma brucei brucei*/metabolism; Membrane Glycoproteins/*metabolism ; Protozoan Proteins/*metabolism; Mammals/metabolism ; Animals ; Complement C3 ; Macrophage-1 Antigen ; Mice |
| Abstract: | African trypanosomes are extracellular pathogens of mammals and are exposed to the adaptive and innate immune systems. Trypanosomes evade the adaptive immune response through antigenic variation, but little is known about how they interact with components of the innate immune response, including complement. Here we demonstrate that an invariant surface glycoprotein, ISG65, is a receptor for complement component 3 (C3). We show how ISG65 binds to the thioester domain of C3b. We also show that C3 contributes to control of trypanosomes during early infection in a mouse model and provide evidence that ISG65 is involved in reducing trypanosome susceptibility to C3-mediated clearance. Deposition of C3b on pathogen surfaces, such as trypanosomes, is a central point in activation of the complement system. In ISG65, trypanosomes have evolved a C3 receptor which diminishes the downstream effects of C3 deposition on the control of infection.; (© 2022. The Author(s).) |
| References: | J Cell Biol. 1997 Oct 6;139(1):103-14. (PMID: 9314532); Acta Crystallogr D Struct Biol. 2018 Feb 1;74(Pt 2):68-84. (PMID: 29533233); Nature. 2005 Sep 22;437(7058):505-11. (PMID: 16177781); Mol Biochem Parasitol. 1995 Jan;69(1):53-63. (PMID: 7723788); Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1905-10. (PMID: 23319650); PLoS Negl Trop Dis. 2013;7(2):e2087. (PMID: 23469310); Bioinformatics. 2016 Sep 1;32(17):i672-i679. (PMID: 27587688); Science. 2010 Dec 24;330(6012):1816-20. (PMID: 21205667); Nat Immunol. 2007 Apr;8(4):430-7. (PMID: 17351618); PLoS Pathog. 2015 Dec 31;11(12):e1005259. (PMID: 26719972); Nat Immunol. 2009 Jul;10(7):721-7. (PMID: 19503103); Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42. (PMID: 21460441); Cell. 2007 Nov 2;131(3):505-15. (PMID: 17981118); Immunol Rev. 2016 Nov;274(1):33-58. (PMID: 27782325); Infect Immun. 1986 Apr;52(1):223-9. (PMID: 3633873); Nature. 2006 Nov 9;444(7116):213-6. (PMID: 17051160); Bioinformatics. 2012 Feb 15;28(4):464-9. (PMID: 22199388); Nat Struct Mol Biol. 2011 Apr;18(4):463-70. (PMID: 21317894); J Biol Chem. 2008 Jun 20;283(25):17579-93. (PMID: 18434316); J Comput Chem. 2004 Oct;25(13):1605-12. (PMID: 15264254); J Biol Chem. 2004 Dec 24;279(52):54887-95. (PMID: 15342636); Immunol Rev. 2016 Nov;274(1):152-171. (PMID: 27782321); Elife. 2014 Dec 12;3:e05553. (PMID: 25497229); Nucleic Acids Res. 2006 May 10;34(9):2495-507. (PMID: 16687655); Nucleic Acids Res. 2018 Jul 2;46(W1):W537-W544. (PMID: 29790989); Front Immunol. 2021 Feb 25;12:602277. (PMID: 33717083); Bioinformatics. 2014 Aug 1;30(15):2114-20. (PMID: 24695404); Bioinformatics. 2013 Jul 15;29(14):1750-7. (PMID: 23681122); J Biol Chem. 1992 May 25;267(15):10797-803. (PMID: 1587856); Science. 2008 May 2;320(5876):677-81. (PMID: 18451305); PLoS Negl Trop Dis. 2018 Apr 2;12(4):e0006388. (PMID: 29608569); Ann Soc Belg Med Trop. 1975;55(1):1-23. (PMID: 1231658); Protein Sci. 2013 Feb;22(2):204-12. (PMID: 23184394); Nat Struct Mol Biol. 2017 Aug;24(8):643-651. (PMID: 28671664); Infect Immun. 1993 Nov;61(11):4540-5. (PMID: 8406850); Science. 1998 May 22;280(5367):1277-81. (PMID: 9596584); Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501. (PMID: 20383002); PLoS Negl Trop Dis. 2014 Dec 18;8(12):e3349. (PMID: 25522322); Nat Rev Microbiol. 2008 Feb;6(2):132-42. (PMID: 18197169); Nat Methods. 2018 Mar;15(3):191-193. (PMID: 29377013); Nat Microbiol. 2019 Dec;4(12):2074-2081. (PMID: 31636418); Nat Methods. 2012 Mar 04;9(4):357-9. (PMID: 22388286); Proteomics. 2011 Jul;11(14):2790-7. (PMID: 21656681); Science. 2005 Jul 15;309(5733):416-22. (PMID: 16020726); Mol Biochem Parasitol. 2011 Feb;175(2):201-4. (PMID: 21074579); J Biol Chem. 1993 Apr 15;268(11):8085-95. (PMID: 8463323); J Appl Crystallogr. 2021 Feb 01;54(Pt 1):343-355. (PMID: 33833657); Parasitology. 2010 Dec;137(14):2029-39. (PMID: 20109254); J Synchrotron Radiat. 2020 Sep 1;27(Pt 5):1438-1446. (PMID: 32876621); Biochemistry. 2000 Aug 8;39(31):9466-76. (PMID: 10924142); Nat Immunol. 2009 Jul;10(7):728-33. (PMID: 19503104); Vet Immunol Immunopathol. 1993 Sep;38(1-2):169-81. (PMID: 8256435); Cell. 1994 Jul 15;78(1):75-86. (PMID: 8033214); Science. 2015 Mar 27;347(6229):1470-3. (PMID: 25814582); J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674. (PMID: 19461840); Eur J Cell Biol. 1994 Jun;64(1):78-87. (PMID: 7957316); Nat Commun. 2020 Mar 12;11(1):1326. (PMID: 32165615); Acta Crystallogr D Struct Biol. 2018 Feb 1;74(Pt 2):85-97. (PMID: 29533234); Nat Commun. 2018 Dec 14;9(1):5316. (PMID: 30552328); Immunol Rev. 2016 Nov;274(1):59-73. (PMID: 27782336); J Struct Biol. 2007 Jan;157(1):281-7. (PMID: 16963278); EMBO J. 2016 May 17;35(10):1133-49. (PMID: 27013439); J Biol Chem. 2007 Oct 12;282(41):30051-61. (PMID: 17699522); PLoS One. 2012;7(4):e35167. (PMID: 22511983); Nature. 2018 Nov;563(7729):121-125. (PMID: 30333624); R Soc Open Sci. 2017 May 3;4(5):170095. (PMID: 28573017) |
| Grant Information: | United Kingdom WT_ Wellcome Trust; 101020/Z/13/Z United Kingdom WT_ Wellcome Trust; MR/P001424/1 United Kingdom MRC_ Medical Research Council; 217138/Z/19/Z United Kingdom WT_ Wellcome Trust |
| Substance Nomenclature: | 0 (Complement C3); 0 (Macrophage-1 Antigen); 0 (Membrane Glycoproteins); 0 (Protozoan Proteins); 147338-68-9 (ISG65 protein, Trypanosoma brucei) |
| Entry Date(s): | Date Created: 20220829 Date Completed: 20220831 Latest Revision: 20251031 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC9424271 |
| DOI: | 10.1038/s41467-022-32728-9 |
| PMID: | 36038546 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't