Structural similarities between the metacyclic and bloodstream form variant surface glycoproteins of the African trypanosome.
| Title: | Structural similarities between the metacyclic and bloodstream form variant surface glycoproteins of the African trypanosome. |
|---|---|
| Authors: | Chandra M; Division of Structural Biology of Infection and Immunity, German Cancer Research Center, Heidelberg, Germany.; Division of Immune Diversity, German Cancer Research Center, Heidelberg, Germany.; Đaković S; Division of Structural Biology of Infection and Immunity, German Cancer Research Center, Heidelberg, Germany.; Foti K; Division of Structural Biology of Infection and Immunity, German Cancer Research Center, Heidelberg, Germany.; Zeelen JP; Division of Structural Biology of Infection and Immunity, German Cancer Research Center, Heidelberg, Germany.; van Straaten M; Division of Structural Biology of Infection and Immunity, German Cancer Research Center, Heidelberg, Germany.; Aresta-Branco F; Division of Structural Biology of Infection and Immunity, German Cancer Research Center, Heidelberg, Germany.; Division of Immune Diversity, German Cancer Research Center, Heidelberg, Germany.; Tihon E; Institut Pasteur, Université Paris Cité, Trypanosome Molecular Biology, Department of Parasites and Insect Vectors, Paris, France.; Lübbehusen N; Centre for Molecular Biology at the University of Heidelberg (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.; Ruppert T; Centre for Molecular Biology at the University of Heidelberg (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.; Glover L; Institut Pasteur, Université Paris Cité, Trypanosome Molecular Biology, Department of Parasites and Insect Vectors, Paris, France.; Papavasiliou FN; Division of Immune Diversity, German Cancer Research Center, Heidelberg, Germany.; Stebbins CE; Division of Structural Biology of Infection and Immunity, German Cancer Research Center, Heidelberg, Germany. |
| Source: | PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2023 Feb 13; Vol. 17 (2), pp. e0011093. Date of Electronic Publication: 2023 Feb 13 (Print Publication: 2023). |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101291488 Publication Model: eCollection Cited Medium: Internet ISSN: 1935-2735 (Electronic) Linking ISSN: 19352727 NLM ISO Abbreviation: PLoS Negl Trop Dis Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: San Francisco, CA : Public Library of Science |
| MeSH Terms: | Trypanosoma brucei brucei*/genetics ; Tsetse Flies*/parasitology ; Trypanosomiasis, African*/parasitology ; Trypanosoma*; Membrane Glycoproteins/metabolism ; Variant Surface Glycoproteins, Trypanosoma/genetics ; Animals ; Mammals |
| Abstract: | During infection of mammalian hosts, African trypanosomes thwart immunity using antigenic variation of the dense Variant Surface Glycoprotein (VSG) coat, accessing a large repertoire of several thousand genes and pseudogenes, and switching to antigenically distinct copies. The parasite is transferred to mammalian hosts by the tsetse fly. In the salivary glands of the fly, the pathogen adopts the metacyclic form and expresses a limited repertoire of VSG genes specific to that developmental stage. It has remained unknown whether the metacyclic VSGs possess distinct properties associated with this particular and discrete phase of the parasite life cycle. We present here three novel metacyclic form VSG N-terminal domain crystal structures (mVSG397, mVSG531, and mVSG1954) and show that they mirror closely in architecture, oligomerization, and surface diversity the known classes of bloodstream form VSGs. These data suggest that the mVSGs are unlikely to be a specialized subclass of VSG proteins, and thus could be poor candidates as the major components of prophylactic vaccines against trypanosomiasis.; (Copyright: © 2023 Chandra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) |
| Competing Interests: | The authors have declared that no competing interests exist. |
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| Substance Nomenclature: | 0 (Membrane Glycoproteins); 0 (Variant Surface Glycoproteins, Trypanosoma) |
| Entry Date(s): | Date Created: 20230213 Date Completed: 20230228 Latest Revision: 20240913 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC9956791 |
| DOI: | 10.1371/journal.pntd.0011093 |
| PMID: | 36780870 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't