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Architecture of a host–parasite interface: complex targeting mechanisms revealed through proteomics

Gadelha, Catarina; Zhang, Wenzhu; Chamberlain, James W.; Chait, Brian T.; Wickstead, Bill; Field, Mark C.

Authors

Wenzhu Zhang

James W. Chamberlain

Brian T. Chait

Mark C. Field



Abstract

Surface membrane organization and composition is key to cellular function, and membrane proteins serve many essential roles in endocytosis, secretion, and cell recognition. The surface of parasitic organisms, however, is a double-edged sword; this is the primary interface between parasites and their hosts, and those crucial cellular processes must be carried out while avoiding elimination by the host immune defenses. For extracellular African trypanosomes, the surface is partitioned such that all endo- and exocytosis is directed through a specific membrane region, the flagellar pocket, in which it is thought the majority of invariant surface proteins reside. However, very few of these proteins have been identified, severely limiting functional studies, and hampering the development of potential treatments. Here we used an integrated biochemical, proteomic and bioinformatic strategy to identify surface components of the human parasite Trypanosoma brucei. This surface proteome contains previously known flagellar pocket proteins as well as multiple novel components, and is significantly enriched in proteins that are essential for parasite survival. Molecules with receptor-like properties are almost exclusively parasite-specific, whereas transporter-like proteins are conserved in model organisms. Validation shows that the majority of surface proteome constituents are bona fide surface-associated proteins and, as expected, most present at the flagellar pocket. Moreover, the largest systematic analysis of trypanosome surface molecules to date provides evidence that the cell surface is compartmentalized into three distinct domains with free diffusion of molecules in each, but selective, asymmetric traffic between. This work provides a paradigm for the compartmentalization of a cell surface and a resource for its analysis.

Citation

Gadelha, C., Zhang, W., Chamberlain, J. W., Chait, B. T., Wickstead, B., & Field, M. C. (2015). Architecture of a host–parasite interface: complex targeting mechanisms revealed through proteomics. Molecular and Cellular Proteomics, 14(7), https://doi.org/10.1074/mcp.M114.047647

Journal Article Type Article
Acceptance Date Apr 22, 2015
Online Publication Date Apr 30, 2015
Publication Date Jul 1, 2015
Deposit Date Mar 21, 2016
Publicly Available Date Mar 21, 2016
Journal Molecular and Cellular Proteomics
Print ISSN 1535-9476
Electronic ISSN 1535-9484
Publisher American Society for Biochemistry and Molecular Biology
Peer Reviewed Peer Reviewed
Volume 14
Issue 7
DOI https://doi.org/10.1074/mcp.M114.047647
Public URL http://eprints.nottingham.ac.uk/id/eprint/32417
Publisher URL http://www.mcponline.org/content/14/7/1911
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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