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dc.contributor.authorSheiner, Lilach
dc.contributor.authorDemerly, Jessica L.
dc.contributor.authorPoulsen, Nicole
dc.contributor.authorBeatty, Wandy L.
dc.contributor.authorLucas, Olivier
dc.contributor.authorBehnke, Michael S.
dc.contributor.authorWhite, Michael W.
dc.contributor.authorStriepen, Boris
dc.date.accessioned2019-04-22T19:33:17Z
dc.date.available2019-04-22T19:33:17Z
dc.date.issued2011-12
dc.identifier.citationSheiner, Lilach, Jessica L. Demerly, Nicole Poulsen, Wandy L. Beatty, Olivier Lucas, Michael S. Behnke, Michael W. White, and Boris Striepen. “A Systematic Screen to Discover and Analyze Apicoplast Proteins Identifies a Conserved and Essential Protein Import Factor.” Edited by Vern B. Carruthers. PLoS Pathogens 7, no. 12 (December 1, 2011): e1002392. doi:10.1371/journal.ppat.1002392.en_US
dc.identifier.issn1553-7374
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/15452
dc.description.abstractParasites of the phylum Apicomplexa cause diseases that impact global health and economy. These unicellular eukaryotes possess a relict plastid, the apicoplast, which is an essential organelle and a validated drug target. However, much of its biology remains poorly understood, in particular its elaborate compartmentalization: four membranes defining four different spaces. Only a small number of organellar proteins have been identified in particular few proteins are known for non-luminal apicoplast compartments. We hypothesized that enlarging the catalogue of apicoplast proteins will contribute toward identifying new organellar functions and expand the realm of targets beyond a limited set of characterized pathways. We developed a bioinformatic screen based on mRNA abundance over the cell cycle and on phyletic distribution. We experimentally assessed 57 genes, and of 30 successful epitope tagged candidates eleven novel apicoplast proteins were identified. Of those, seven appear to target to the lumen of the organelle, and four localize to peripheral compartments. To address their function we then developed a robust system for the construction of conditional mutants via a promoter replacement strategy. We confirm the feasibility of this system by establishing conditional mutants for two selected genes – a luminal and a peripheral apicoplast protein. The latter is particularly intriguing as it encodes a hypothetical protein that is conserved in and unique to Apicomplexan parasites and other related organisms that maintain a red algal endosymbiont. Our studies suggest that this peripheral plastid protein, PPP1, is likely localized to the periplastid compartment. Conditional disruption of PPP1 demonstrated that it is essential for parasite survival. Phenotypic analysis of this mutant is consistent with a role of the PPP1 protein in apicoplast biogenesis, specifically in import of nuclear-encoded proteins into the organelle.en_US
dc.description.sponsorshipNational Institutes of Health grants AI084415, AI64671; Swiss National Funden_US
dc.language.isoenen_US
dc.rightsCC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/legalcodeen_US
dc.titleA systematic screen to discover and analyze apicoplast proteins identifies a conserved and essential protein import factoren_US
dc.typeArticleen_US
mus.citation.issue12en_US
mus.citation.journaltitlePLoS Pathogensen_US
mus.citation.volume7en_US
mus.identifier.categoryLife Sciences & Earth Sciencesen_US
mus.identifier.doi10.1371/journal.ppat.1002392en_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.relation.researchgroupMT INBRE Bioinformatics and Biostatistics Core.en_US
mus.data.thumbpage7en_US


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CC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.
Except where otherwise noted, this item's license is described as CC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.

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