How Does the VSG Coat of Bloodstream Form African Trypanosomes Interact with External Proteins?
Variations on the statement "the variant surface glycoprotein (VSG) coat that covers the external face of the mammalian bloodstream form of Trypanosoma brucei acts a physical barrier" appear regularly in research articles and reviews. The concept of the impenetrable VSG coat is an attracti...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-12-01
|
| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC4697842?pdf=render |
| _version_ | 1828438134142009344 |
|---|---|
| author | Angela Schwede Olivia J S Macleod Paula MacGregor Mark Carrington |
| author_facet | Angela Schwede Olivia J S Macleod Paula MacGregor Mark Carrington |
| author_sort | Angela Schwede |
| collection | DOAJ |
| description | Variations on the statement "the variant surface glycoprotein (VSG) coat that covers the external face of the mammalian bloodstream form of Trypanosoma brucei acts a physical barrier" appear regularly in research articles and reviews. The concept of the impenetrable VSG coat is an attractive one, as it provides a clear model for understanding how a trypanosome population persists; each successive VSG protects the plasma membrane and is immunologically distinct from previous VSGs. What is the evidence that the VSG coat is an impenetrable barrier, and how do antibodies and other extracellular proteins interact with it? In this review, the nature of the extracellular surface of the bloodstream form trypanosome is described, and past experiments that investigated binding of antibodies and lectins to trypanosomes are analysed using knowledge of VSG sequence and structure that was unavailable when the experiments were performed. Epitopes for some VSG monoclonal antibodies are mapped as far as possible from previous experimental data, onto models of VSG structures. The binding of lectins to some, but not to other, VSGs is revisited with more recent knowledge of the location and nature of N-linked oligosaccharides. The conclusions are: (i) Much of the variation observed in earlier experiments can be explained by the identity of the individual VSGs. (ii) Much of an individual VSG is accessible to antibodies, and the barrier that prevents access to the cell surface is probably at the base of the VSG N-terminal domain, approximately 5 nm from the plasma membrane. This second conclusion highlights a gap in our understanding of how the VSG coat works, as several plasma membrane proteins with large extracellular domains are very unlikely to be hidden from host antibodies by VSG. |
| first_indexed | 2024-12-10T19:58:42Z |
| format | Article |
| id | doaj.art-3f515d02c7404c299624335ccdb65adf |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-10T19:58:42Z |
| publishDate | 2015-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-3f515d02c7404c299624335ccdb65adf2022-12-22T01:35:35ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-12-011112e100525910.1371/journal.ppat.1005259How Does the VSG Coat of Bloodstream Form African Trypanosomes Interact with External Proteins?Angela SchwedeOlivia J S MacleodPaula MacGregorMark CarringtonVariations on the statement "the variant surface glycoprotein (VSG) coat that covers the external face of the mammalian bloodstream form of Trypanosoma brucei acts a physical barrier" appear regularly in research articles and reviews. The concept of the impenetrable VSG coat is an attractive one, as it provides a clear model for understanding how a trypanosome population persists; each successive VSG protects the plasma membrane and is immunologically distinct from previous VSGs. What is the evidence that the VSG coat is an impenetrable barrier, and how do antibodies and other extracellular proteins interact with it? In this review, the nature of the extracellular surface of the bloodstream form trypanosome is described, and past experiments that investigated binding of antibodies and lectins to trypanosomes are analysed using knowledge of VSG sequence and structure that was unavailable when the experiments were performed. Epitopes for some VSG monoclonal antibodies are mapped as far as possible from previous experimental data, onto models of VSG structures. The binding of lectins to some, but not to other, VSGs is revisited with more recent knowledge of the location and nature of N-linked oligosaccharides. The conclusions are: (i) Much of the variation observed in earlier experiments can be explained by the identity of the individual VSGs. (ii) Much of an individual VSG is accessible to antibodies, and the barrier that prevents access to the cell surface is probably at the base of the VSG N-terminal domain, approximately 5 nm from the plasma membrane. This second conclusion highlights a gap in our understanding of how the VSG coat works, as several plasma membrane proteins with large extracellular domains are very unlikely to be hidden from host antibodies by VSG.http://europepmc.org/articles/PMC4697842?pdf=render |
| spellingShingle | Angela Schwede Olivia J S Macleod Paula MacGregor Mark Carrington How Does the VSG Coat of Bloodstream Form African Trypanosomes Interact with External Proteins? PLoS Pathogens |
| title | How Does the VSG Coat of Bloodstream Form African Trypanosomes Interact with External Proteins? |
| title_full | How Does the VSG Coat of Bloodstream Form African Trypanosomes Interact with External Proteins? |
| title_fullStr | How Does the VSG Coat of Bloodstream Form African Trypanosomes Interact with External Proteins? |
| title_full_unstemmed | How Does the VSG Coat of Bloodstream Form African Trypanosomes Interact with External Proteins? |
| title_short | How Does the VSG Coat of Bloodstream Form African Trypanosomes Interact with External Proteins? |
| title_sort | how does the vsg coat of bloodstream form african trypanosomes interact with external proteins |
| url | http://europepmc.org/articles/PMC4697842?pdf=render |
| work_keys_str_mv | AT angelaschwede howdoesthevsgcoatofbloodstreamformafricantrypanosomesinteractwithexternalproteins AT oliviajsmacleod howdoesthevsgcoatofbloodstreamformafricantrypanosomesinteractwithexternalproteins AT paulamacgregor howdoesthevsgcoatofbloodstreamformafricantrypanosomesinteractwithexternalproteins AT markcarrington howdoesthevsgcoatofbloodstreamformafricantrypanosomesinteractwithexternalproteins |