Dynamic, variable oligomerization and the trafficking of variant surface glycoproteins of Trypanosoma brucei.
glycosylphosphatidylinositol anchor
protein trafficking
trypanosome
valence hypothesis
variant surface glycoprotein
Journal
Traffic (Copenhagen, Denmark)
ISSN: 1600-0854
Titre abrégé: Traffic
Pays: England
ID NLM: 100939340
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
14
05
2021
received:
26
10
2020
accepted:
04
06
2021
pubmed:
9
6
2021
medline:
3
8
2021
entrez:
8
6
2021
Statut:
ppublish
Résumé
African trypanosomes cause disease in humans and livestock, avoiding host immunity by changing the expression of variant surface glycoproteins (VSGs); the major glycosylphosphatidylinositol (GPI) anchored antigens coating the surface of the bloodstream stage. Proper trafficking of VSGs is therefore critical to pathogen survival. The valence model argues that GPI anchors regulate progression and fate in the secretory pathway and that, specifically, a valence of two (VSGs are dimers) is critical for stable cell surface association. However, recent reports that the MITat1.3 (M1.3) VSG N-terminal domain (NTD) behaves as a monomer in solution and in a crystal structure challenge this model. We now show that the behavior of intact M1.3 VSG in standard in vivo trafficking assays is consistent with an oligomer. Nevertheless, Blue Native Gel electrophoresis and size exclusion chromatography-multiangle light scattering chromatography of purified full length M1.3 VSG indicates a monomer in vitro. However, studies with additional VSGs show that multiple oligomeric states are possible, and that for some VSGs oligomerization is concentration dependent. These data argue that individual VSG monomers possess different propensities to self-oligomerize, but that when constrained at high density to the cell surface, oligomeric species predominate. These results resolve the apparent conflict between the valence hypothesis and the M1.3 NTD VSG crystal structure.
Substances chimiques
Glycosylphosphatidylinositols
0
Membrane Glycoproteins
0
Variant Surface Glycoproteins, Trypanosoma
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
274-283Subventions
Organisme : NIAID NIH HHS
ID : R01 AI035739
Pays : United States
Organisme : Deutsches Krebsforschungszentrum
Organisme : Jacobs School of Medicine and Biomedical Sciences
Organisme : NIH HHS
ID : AI035739
Pays : United States
Informations de copyright
© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.
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