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Malaria parasite evades mosquito immunity by glutaminyl cyclase–mediated posttranslational protein modification

Glutaminyl cyclase (QC) modifies N-terminal glutamine or glutamic acid residues of target proteins into cyclic pyroglutamic acid (pGlu). Here, we report the biochemical and functional analysis of Plasmodium QC. We show that sporozoites of QC-null mutants of rodent and human malaria parasites are rec...

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Autores principales: Kolli, Surendra Kumar, Molina-Cruz, Alvaro, Araki, Tamasa, Geurten, Fiona J. A., Ramesar, Jai, Chevalley-Maurel, Severine, Kroeze, Hans J., Bezemer, Sascha, de Korne, Clarize, Withers, Roxanne, Raytselis, Nadia, El Hebieshy, Angela F., Kim, Robbert Q., Child, Matthew A., Kakuta, Soichiro, Hisaeda, Hajime, Kobayashi, Hirotaka, Annoura, Takeshi, Hensbergen, Paul J., Franke-Fayard, Blandine M., Barillas-Mury, Carolina, Scheeren, Ferenc A., Janse, Chris J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436314/
https://www.ncbi.nlm.nih.gov/pubmed/35994647
http://dx.doi.org/10.1073/pnas.2209729119
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author Kolli, Surendra Kumar
Molina-Cruz, Alvaro
Araki, Tamasa
Geurten, Fiona J. A.
Ramesar, Jai
Chevalley-Maurel, Severine
Kroeze, Hans J.
Bezemer, Sascha
de Korne, Clarize
Withers, Roxanne
Raytselis, Nadia
El Hebieshy, Angela F.
Kim, Robbert Q.
Child, Matthew A.
Kakuta, Soichiro
Hisaeda, Hajime
Kobayashi, Hirotaka
Annoura, Takeshi
Hensbergen, Paul J.
Franke-Fayard, Blandine M.
Barillas-Mury, Carolina
Scheeren, Ferenc A.
Janse, Chris J.
author_facet Kolli, Surendra Kumar
Molina-Cruz, Alvaro
Araki, Tamasa
Geurten, Fiona J. A.
Ramesar, Jai
Chevalley-Maurel, Severine
Kroeze, Hans J.
Bezemer, Sascha
de Korne, Clarize
Withers, Roxanne
Raytselis, Nadia
El Hebieshy, Angela F.
Kim, Robbert Q.
Child, Matthew A.
Kakuta, Soichiro
Hisaeda, Hajime
Kobayashi, Hirotaka
Annoura, Takeshi
Hensbergen, Paul J.
Franke-Fayard, Blandine M.
Barillas-Mury, Carolina
Scheeren, Ferenc A.
Janse, Chris J.
author_sort Kolli, Surendra Kumar
collection PubMed
description Glutaminyl cyclase (QC) modifies N-terminal glutamine or glutamic acid residues of target proteins into cyclic pyroglutamic acid (pGlu). Here, we report the biochemical and functional analysis of Plasmodium QC. We show that sporozoites of QC-null mutants of rodent and human malaria parasites are recognized by the mosquito immune system and melanized when they reach the hemocoel. Detailed analyses of rodent malaria QC-null mutants showed that sporozoite numbers in salivary glands are reduced in mosquitoes infected with QC-null or QC catalytically dead mutants. This phenotype can be rescued by genetic complementation or by disrupting mosquito melanization or phagocytosis by hemocytes. Mutation of a single QC-target glutamine of the major sporozoite surface protein (circumsporozoite protein; CSP) of the rodent parasite Plasmodium berghei also results in melanization of sporozoites. These findings indicate that QC-mediated posttranslational modification of surface proteins underlies evasion of killing of sporozoites by the mosquito immune system.
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spelling pubmed-94363142023-02-22 Malaria parasite evades mosquito immunity by glutaminyl cyclase–mediated posttranslational protein modification Kolli, Surendra Kumar Molina-Cruz, Alvaro Araki, Tamasa Geurten, Fiona J. A. Ramesar, Jai Chevalley-Maurel, Severine Kroeze, Hans J. Bezemer, Sascha de Korne, Clarize Withers, Roxanne Raytselis, Nadia El Hebieshy, Angela F. Kim, Robbert Q. Child, Matthew A. Kakuta, Soichiro Hisaeda, Hajime Kobayashi, Hirotaka Annoura, Takeshi Hensbergen, Paul J. Franke-Fayard, Blandine M. Barillas-Mury, Carolina Scheeren, Ferenc A. Janse, Chris J. Proc Natl Acad Sci U S A Biological Sciences Glutaminyl cyclase (QC) modifies N-terminal glutamine or glutamic acid residues of target proteins into cyclic pyroglutamic acid (pGlu). Here, we report the biochemical and functional analysis of Plasmodium QC. We show that sporozoites of QC-null mutants of rodent and human malaria parasites are recognized by the mosquito immune system and melanized when they reach the hemocoel. Detailed analyses of rodent malaria QC-null mutants showed that sporozoite numbers in salivary glands are reduced in mosquitoes infected with QC-null or QC catalytically dead mutants. This phenotype can be rescued by genetic complementation or by disrupting mosquito melanization or phagocytosis by hemocytes. Mutation of a single QC-target glutamine of the major sporozoite surface protein (circumsporozoite protein; CSP) of the rodent parasite Plasmodium berghei also results in melanization of sporozoites. These findings indicate that QC-mediated posttranslational modification of surface proteins underlies evasion of killing of sporozoites by the mosquito immune system. National Academy of Sciences 2022-08-22 2022-08-30 /pmc/articles/PMC9436314/ /pubmed/35994647 http://dx.doi.org/10.1073/pnas.2209729119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Kolli, Surendra Kumar
Molina-Cruz, Alvaro
Araki, Tamasa
Geurten, Fiona J. A.
Ramesar, Jai
Chevalley-Maurel, Severine
Kroeze, Hans J.
Bezemer, Sascha
de Korne, Clarize
Withers, Roxanne
Raytselis, Nadia
El Hebieshy, Angela F.
Kim, Robbert Q.
Child, Matthew A.
Kakuta, Soichiro
Hisaeda, Hajime
Kobayashi, Hirotaka
Annoura, Takeshi
Hensbergen, Paul J.
Franke-Fayard, Blandine M.
Barillas-Mury, Carolina
Scheeren, Ferenc A.
Janse, Chris J.
Malaria parasite evades mosquito immunity by glutaminyl cyclase–mediated posttranslational protein modification
title Malaria parasite evades mosquito immunity by glutaminyl cyclase–mediated posttranslational protein modification
title_full Malaria parasite evades mosquito immunity by glutaminyl cyclase–mediated posttranslational protein modification
title_fullStr Malaria parasite evades mosquito immunity by glutaminyl cyclase–mediated posttranslational protein modification
title_full_unstemmed Malaria parasite evades mosquito immunity by glutaminyl cyclase–mediated posttranslational protein modification
title_short Malaria parasite evades mosquito immunity by glutaminyl cyclase–mediated posttranslational protein modification
title_sort malaria parasite evades mosquito immunity by glutaminyl cyclase–mediated posttranslational protein modification
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436314/
https://www.ncbi.nlm.nih.gov/pubmed/35994647
http://dx.doi.org/10.1073/pnas.2209729119
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