Journal Article

DKFZ-2021-01276

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dynamic, Variable Oligomerization and the Trafficking of Variant Surface Glycoproteins of Trypanosoma brucei.

Umaer, K. ; Aresta-Branco, F.DKFZ* ; Chandra, M.DKFZ* ; van Straaten, M.DKFZ* ; Zeelen, J.DKFZ* ; Lapouge, K. ; Waxman, B. ; Stebbins, C. E.DKFZ* ; Bangs, J. D.

2021
Wiley-Blackwell Oxford

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Please use a persistent id in citations: doi:10.1111/tra.12806

Abstract: 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 structure1 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 SEC-MALS 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. This article is protected by copyright. All rights reserved.

Keyword(s): glycosylphosphatidylinositol anchor ; protein trafficking ; trypanosome ; valence hypothesis ; variant surface glycoprotein

Note: 2021 Aug;22(8):274-283

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Contributing Institute(s):

1. D160 Strukturbiologie von Infektion und Immunität (D160)
2. D150 Immundiversität (D150)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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