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Rab1-AMPylation by Legionella DrrA is allosterically activated by Rab1

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Rab1-AMPylation by Legionella DrrA is allosterically activated by Rab1. / Du, Jiqing; Wrisberg, Marie-Kristin von; Gulen, Burak; Stahl, Matthias; Pett, Christian; Hedberg, Christian; Lang, Kathrin; Schneider, Sabine; Itzen, Aymelt.

In: NAT COMMUN, Vol. 12, No. 1, 460, 19.01.2021.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Du, J, Wrisberg, M-KV, Gulen, B, Stahl, M, Pett, C, Hedberg, C, Lang, K, Schneider, S & Itzen, A 2021, 'Rab1-AMPylation by Legionella DrrA is allosterically activated by Rab1', NAT COMMUN, vol. 12, no. 1, 460. https://doi.org/10.1038/s41467-020-20702-2

APA

Du, J., Wrisberg, M-K. V., Gulen, B., Stahl, M., Pett, C., Hedberg, C., Lang, K., Schneider, S., & Itzen, A. (2021). Rab1-AMPylation by Legionella DrrA is allosterically activated by Rab1. NAT COMMUN, 12(1), [460]. https://doi.org/10.1038/s41467-020-20702-2

Vancouver

Du J, Wrisberg M-KV, Gulen B, Stahl M, Pett C, Hedberg C et al. Rab1-AMPylation by Legionella DrrA is allosterically activated by Rab1. NAT COMMUN. 2021 Jan 19;12(1). 460. https://doi.org/10.1038/s41467-020-20702-2

Bibtex

@article{2663f50ee60d4142afd6c3645225e5c3,
title = "Rab1-AMPylation by Legionella DrrA is allosterically activated by Rab1",
abstract = "Legionella pneumophila infects eukaryotic cells by forming a replicative organelle - the Legionella containing vacuole. During this process, the bacterial protein DrrA/SidM is secreted and manipulates the activity and post-translational modification (PTM) states of the vesicular trafficking regulator Rab1. As a result, Rab1 is modified with an adenosine monophosphate (AMP), and this process is referred to as AMPylation. Here, we use a chemical approach to stabilise low-affinity Rab:DrrA complexes in a site-specific manner to gain insight into the molecular basis of the interaction between the Rab protein and the AMPylation domain of DrrA. The crystal structure of the Rab:DrrA complex reveals a previously unknown non-conventional Rab-binding site (NC-RBS). Biochemical characterisation demonstrates allosteric stimulation of the AMPylation activity of DrrA via Rab binding to the NC-RBS. We speculate that allosteric control of DrrA could in principle prevent random and potentially cytotoxic AMPylation in the host, thereby perhaps ensuring efficient infection by Legionella.",
keywords = "Adenosine Monophosphate/metabolism, Allosteric Regulation, Bacterial Proteins/genetics, Binding Sites/genetics, Crystallography, X-Ray, Guanine Nucleotide Exchange Factors/genetics, Guanosine Triphosphate/metabolism, Humans, Legionella pneumophila/metabolism, Legionnaires' Disease/microbiology, Macrophages, Alveolar/metabolism, Phagocytosis, Protein Binding, Protein Processing, Post-Translational, Recombinant Proteins/genetics, rab1 GTP-Binding Proteins/genetics",
author = "Jiqing Du and Wrisberg, {Marie-Kristin von} and Burak Gulen and Matthias Stahl and Christian Pett and Christian Hedberg and Kathrin Lang and Sabine Schneider and Aymelt Itzen",
year = "2021",
month = jan,
day = "19",
doi = "10.1038/s41467-020-20702-2",
language = "English",
volume = "12",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Rab1-AMPylation by Legionella DrrA is allosterically activated by Rab1

AU - Du, Jiqing

AU - Wrisberg, Marie-Kristin von

AU - Gulen, Burak

AU - Stahl, Matthias

AU - Pett, Christian

AU - Hedberg, Christian

AU - Lang, Kathrin

AU - Schneider, Sabine

AU - Itzen, Aymelt

PY - 2021/1/19

Y1 - 2021/1/19

N2 - Legionella pneumophila infects eukaryotic cells by forming a replicative organelle - the Legionella containing vacuole. During this process, the bacterial protein DrrA/SidM is secreted and manipulates the activity and post-translational modification (PTM) states of the vesicular trafficking regulator Rab1. As a result, Rab1 is modified with an adenosine monophosphate (AMP), and this process is referred to as AMPylation. Here, we use a chemical approach to stabilise low-affinity Rab:DrrA complexes in a site-specific manner to gain insight into the molecular basis of the interaction between the Rab protein and the AMPylation domain of DrrA. The crystal structure of the Rab:DrrA complex reveals a previously unknown non-conventional Rab-binding site (NC-RBS). Biochemical characterisation demonstrates allosteric stimulation of the AMPylation activity of DrrA via Rab binding to the NC-RBS. We speculate that allosteric control of DrrA could in principle prevent random and potentially cytotoxic AMPylation in the host, thereby perhaps ensuring efficient infection by Legionella.

AB - Legionella pneumophila infects eukaryotic cells by forming a replicative organelle - the Legionella containing vacuole. During this process, the bacterial protein DrrA/SidM is secreted and manipulates the activity and post-translational modification (PTM) states of the vesicular trafficking regulator Rab1. As a result, Rab1 is modified with an adenosine monophosphate (AMP), and this process is referred to as AMPylation. Here, we use a chemical approach to stabilise low-affinity Rab:DrrA complexes in a site-specific manner to gain insight into the molecular basis of the interaction between the Rab protein and the AMPylation domain of DrrA. The crystal structure of the Rab:DrrA complex reveals a previously unknown non-conventional Rab-binding site (NC-RBS). Biochemical characterisation demonstrates allosteric stimulation of the AMPylation activity of DrrA via Rab binding to the NC-RBS. We speculate that allosteric control of DrrA could in principle prevent random and potentially cytotoxic AMPylation in the host, thereby perhaps ensuring efficient infection by Legionella.

KW - Adenosine Monophosphate/metabolism

KW - Allosteric Regulation

KW - Bacterial Proteins/genetics

KW - Binding Sites/genetics

KW - Crystallography, X-Ray

KW - Guanine Nucleotide Exchange Factors/genetics

KW - Guanosine Triphosphate/metabolism

KW - Humans

KW - Legionella pneumophila/metabolism

KW - Legionnaires' Disease/microbiology

KW - Macrophages, Alveolar/metabolism

KW - Phagocytosis

KW - Protein Binding

KW - Protein Processing, Post-Translational

KW - Recombinant Proteins/genetics

KW - rab1 GTP-Binding Proteins/genetics

U2 - 10.1038/s41467-020-20702-2

DO - 10.1038/s41467-020-20702-2

M3 - SCORING: Journal article

C2 - 33469029

VL - 12

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

M1 - 460

ER -