Divergent Evolution of <italic toggle="yes">Legionella</italic> RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets

ABSTRACT Legionella pneumophila governs its interactions with host cells by secreting >300 different “effector” proteins. Some of these effectors contain eukaryotic domains such as the RCC1 (regulator of chromosome condensation 1) repeats promoting the activation of the small GTPase Ran. In this...

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Autores principales:	A. Leoni Swart, Bernhard Steiner, Laura Gomez-Valero, Sabina Schütz, Mandy Hannemann, Petra Janning, Michael Irminger, Eva Rothmeier, Carmen Buchrieser, Aymelt Itzen, Vikram Govind Panse, Hubert Hilbi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	amoeba bacterial evolution Acanthamoeba Dictyostelium effector protein guanine nucleotide exchange factor Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b6a4a85bf46b4fbaa5aaf3dcedc0ad39
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spelling	oai:doaj.org-article:b6a4a85bf46b4fbaa5aaf3dcedc0ad392021-11-15T15:57:03ZDivergent Evolution of <italic toggle="yes">Legionella</italic> RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets10.1128/mBio.00405-202150-7511https://doaj.org/article/b6a4a85bf46b4fbaa5aaf3dcedc0ad392020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00405-20https://doaj.org/toc/2150-7511ABSTRACT Legionella pneumophila governs its interactions with host cells by secreting >300 different “effector” proteins. Some of these effectors contain eukaryotic domains such as the RCC1 (regulator of chromosome condensation 1) repeats promoting the activation of the small GTPase Ran. In this report, we reveal a conserved pattern of L. pneumophila RCC1 repeat genes, which are distributed in two main clusters of strains. Accordingly, strain Philadelphia-1 contains two RCC1 genes implicated in bacterial virulence, legG1 (Legionella eukaryotic gene 1), and ppgA, while strain Paris contains only one, pieG. The RCC1 repeat effectors localize to different cellular compartments and bind distinct components of the Ran GTPase cycle, including Ran modulators and the small GTPase itself, and yet they all promote the activation of Ran. The pieG gene spans the corresponding open reading frames of legG1 and a separate adjacent upstream gene, lpg1975. legG1 and lpg1975 are fused upon addition of a single nucleotide to encode a protein that adopts the binding specificity of PieG. Thus, a point mutation in pieG splits the gene, altering the effector target. These results indicate that divergent evolution of RCC1 repeat effectors defines the Ran GTPase cycle targets and that modulation of different components of the cycle might fine-tune Ran activation during Legionella infection. IMPORTANCE Legionella pneumophila is a ubiquitous environmental bacterium which, upon inhalation, causes a life-threatening pneumonia termed Legionnaires’ disease. The opportunistic pathogen grows in amoebae and macrophages by employing a “type IV” secretion system, which secretes more than 300 different “effector” proteins into the host cell, where they subvert pivotal processes. The function of many of these effector proteins is unknown, and their evolution has not been studied. L. pneumophila RCC1 repeat effectors target the small GTPase Ran, a molecular switch implicated in different cellular processes such as nucleocytoplasmic transport and microtubule cytoskeleton dynamics. We provide evidence that one or more RCC1 repeat genes are distributed in two main clusters of L. pneumophila strains and have divergently evolved to target different components of the Ran GTPase activation cycle at different subcellular sites. Thus, L. pneumophila employs a sophisticated strategy to subvert host cell Ran GTPase during infection.A. Leoni SwartBernhard SteinerLaura Gomez-ValeroSabina SchützMandy HannemannPetra JanningMichael IrmingerEva RothmeierCarmen BuchrieserAymelt ItzenVikram Govind PanseHubert HilbiAmerican Society for Microbiologyarticleamoebabacterial evolutionAcanthamoebaDictyosteliumeffector proteinguanine nucleotide exchange factorMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	amoeba bacterial evolution Acanthamoeba Dictyostelium effector protein guanine nucleotide exchange factor Microbiology QR1-502
spellingShingle	amoeba bacterial evolution Acanthamoeba Dictyostelium effector protein guanine nucleotide exchange factor Microbiology QR1-502 A. Leoni Swart Bernhard Steiner Laura Gomez-Valero Sabina Schütz Mandy Hannemann Petra Janning Michael Irminger Eva Rothmeier Carmen Buchrieser Aymelt Itzen Vikram Govind Panse Hubert Hilbi Divergent Evolution of <italic toggle="yes">Legionella</italic> RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets
description	ABSTRACT Legionella pneumophila governs its interactions with host cells by secreting >300 different “effector” proteins. Some of these effectors contain eukaryotic domains such as the RCC1 (regulator of chromosome condensation 1) repeats promoting the activation of the small GTPase Ran. In this report, we reveal a conserved pattern of L. pneumophila RCC1 repeat genes, which are distributed in two main clusters of strains. Accordingly, strain Philadelphia-1 contains two RCC1 genes implicated in bacterial virulence, legG1 (Legionella eukaryotic gene 1), and ppgA, while strain Paris contains only one, pieG. The RCC1 repeat effectors localize to different cellular compartments and bind distinct components of the Ran GTPase cycle, including Ran modulators and the small GTPase itself, and yet they all promote the activation of Ran. The pieG gene spans the corresponding open reading frames of legG1 and a separate adjacent upstream gene, lpg1975. legG1 and lpg1975 are fused upon addition of a single nucleotide to encode a protein that adopts the binding specificity of PieG. Thus, a point mutation in pieG splits the gene, altering the effector target. These results indicate that divergent evolution of RCC1 repeat effectors defines the Ran GTPase cycle targets and that modulation of different components of the cycle might fine-tune Ran activation during Legionella infection. IMPORTANCE Legionella pneumophila is a ubiquitous environmental bacterium which, upon inhalation, causes a life-threatening pneumonia termed Legionnaires’ disease. The opportunistic pathogen grows in amoebae and macrophages by employing a “type IV” secretion system, which secretes more than 300 different “effector” proteins into the host cell, where they subvert pivotal processes. The function of many of these effector proteins is unknown, and their evolution has not been studied. L. pneumophila RCC1 repeat effectors target the small GTPase Ran, a molecular switch implicated in different cellular processes such as nucleocytoplasmic transport and microtubule cytoskeleton dynamics. We provide evidence that one or more RCC1 repeat genes are distributed in two main clusters of L. pneumophila strains and have divergently evolved to target different components of the Ran GTPase activation cycle at different subcellular sites. Thus, L. pneumophila employs a sophisticated strategy to subvert host cell Ran GTPase during infection.
format	article
author	A. Leoni Swart Bernhard Steiner Laura Gomez-Valero Sabina Schütz Mandy Hannemann Petra Janning Michael Irminger Eva Rothmeier Carmen Buchrieser Aymelt Itzen Vikram Govind Panse Hubert Hilbi
author_facet	A. Leoni Swart Bernhard Steiner Laura Gomez-Valero Sabina Schütz Mandy Hannemann Petra Janning Michael Irminger Eva Rothmeier Carmen Buchrieser Aymelt Itzen Vikram Govind Panse Hubert Hilbi
author_sort	A. Leoni Swart
title	Divergent Evolution of <italic toggle="yes">Legionella</italic> RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets
title_short	Divergent Evolution of <italic toggle="yes">Legionella</italic> RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets
title_full	Divergent Evolution of <italic toggle="yes">Legionella</italic> RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets
title_fullStr	Divergent Evolution of <italic toggle="yes">Legionella</italic> RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets
title_full_unstemmed	Divergent Evolution of <italic toggle="yes">Legionella</italic> RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets
title_sort	divergent evolution of <italic toggle="yes">legionella</italic> rcc1 repeat effectors defines the range of ran gtpase cycle targets
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/b6a4a85bf46b4fbaa5aaf3dcedc0ad39
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Divergent Evolution of <italic toggle="yes">Legionella</italic> RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets

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