Insights into the ubiquitin transfer cascade catalyzed by the Legionella effector SidC

The causative agent of Legionnaires’ disease, Legionella pneumophila, delivers more than 330 virulent effectors to its host to establish an intracellular membrane-bound organelle called the Legionella containing vacuole. Among the army of Legionella effectors, SidC and its paralog SdcA have been ide...

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Main Authors: David Jon Wasilko, Qingqiu Huang, Yuxin Mao
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-07-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/36154
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author David Jon Wasilko
Qingqiu Huang
Yuxin Mao
author_facet David Jon Wasilko
Qingqiu Huang
Yuxin Mao
author_sort David Jon Wasilko
collection DOAJ
description The causative agent of Legionnaires’ disease, Legionella pneumophila, delivers more than 330 virulent effectors to its host to establish an intracellular membrane-bound organelle called the Legionella containing vacuole. Among the army of Legionella effectors, SidC and its paralog SdcA have been identified as novel bacterial ubiquitin (Ub) E3 ligases. To gain insight into the molecular mechanism of SidC/SdcA as Ub ligases, we determined the crystal structures of a binary complex of the N-terminal catalytic SNL domain of SdcA with its cognate E2 UbcH5C and a ternary complex consisting of the SNL domain of SidC with the Ub-linked E2 UbcH7. These two structures reveal the molecular determinants governing the Ub transfer cascade catalyzed by SidC. Together, our data support a common mechanism in the Ub transfer cascade in which the donor Ub is immobilized with its C-terminal tail locked in an extended conformation, priming the donor Ub for catalysis.
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spelling doaj.art-9a3213f177ec463faaf1f5add6a7b0b72022-12-22T03:24:41ZengeLife Sciences Publications LtdeLife2050-084X2018-07-01710.7554/eLife.36154Insights into the ubiquitin transfer cascade catalyzed by the Legionella effector SidCDavid Jon Wasilko0https://orcid.org/0000-0002-6227-5902Qingqiu Huang1Yuxin Mao2https://orcid.org/0000-0002-5064-1397Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United StatesMacCHESS, Cornell University, Ithaca, United StatesDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, United States; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United StatesThe causative agent of Legionnaires’ disease, Legionella pneumophila, delivers more than 330 virulent effectors to its host to establish an intracellular membrane-bound organelle called the Legionella containing vacuole. Among the army of Legionella effectors, SidC and its paralog SdcA have been identified as novel bacterial ubiquitin (Ub) E3 ligases. To gain insight into the molecular mechanism of SidC/SdcA as Ub ligases, we determined the crystal structures of a binary complex of the N-terminal catalytic SNL domain of SdcA with its cognate E2 UbcH5C and a ternary complex consisting of the SNL domain of SidC with the Ub-linked E2 UbcH7. These two structures reveal the molecular determinants governing the Ub transfer cascade catalyzed by SidC. Together, our data support a common mechanism in the Ub transfer cascade in which the donor Ub is immobilized with its C-terminal tail locked in an extended conformation, priming the donor Ub for catalysis.https://elifesciences.org/articles/36154HECT E3 ligaselegionella pneumophilaUbcH5UbcH7
spellingShingle David Jon Wasilko
Qingqiu Huang
Yuxin Mao
Insights into the ubiquitin transfer cascade catalyzed by the Legionella effector SidC
eLife
HECT E3 ligase
legionella pneumophila
UbcH5
UbcH7
title Insights into the ubiquitin transfer cascade catalyzed by the Legionella effector SidC
title_full Insights into the ubiquitin transfer cascade catalyzed by the Legionella effector SidC
title_fullStr Insights into the ubiquitin transfer cascade catalyzed by the Legionella effector SidC
title_full_unstemmed Insights into the ubiquitin transfer cascade catalyzed by the Legionella effector SidC
title_short Insights into the ubiquitin transfer cascade catalyzed by the Legionella effector SidC
title_sort insights into the ubiquitin transfer cascade catalyzed by the legionella effector sidc
topic HECT E3 ligase
legionella pneumophila
UbcH5
UbcH7
url https://elifesciences.org/articles/36154
work_keys_str_mv AT davidjonwasilko insightsintotheubiquitintransfercascadecatalyzedbythelegionellaeffectorsidc
AT qingqiuhuang insightsintotheubiquitintransfercascadecatalyzedbythelegionellaeffectorsidc
AT yuxinmao insightsintotheubiquitintransfercascadecatalyzedbythelegionellaeffectorsidc