Structural insights into Legionella RidL-Vps29 retromer subunit interaction reveal displacement of the regulator TBC1D5
Author(s)
Type
Journal Article
Abstract
Legionella pneumophila can cause Legionnaires’ disease and replicates intracellularly in a
distinct Legionella-containing vacuole (LCV). LCV formation is a complex process that
involves a plethora of type IV-secreted effector proteins. The effector RidL binds the Vps29
retromer subunit, blocks retrograde vesicle trafficking, and promotes intracellular bacterial
replication. Here, we reveal that the 29-kDa N-terminal domain of RidL (RidL2–281) adopts a
“foot-like” fold comprising a protruding β-hairpin at its “heel”. The deletion of the β-hairpin,
the exchange to Glu of Ile170 in the β-hairpin, or Leu152 in Vps29 abolishes the interaction in
eukaryotic cells and in vitro. RidL2–281 or RidL displace the Rab7 GTPase-activating protein
(GAP) TBC1D5 from the retromer and LCVs, respectively, and TBC1D5 promotes the
intracellular growth of L. pneumophila. Thus, the hydrophobic β-hairpin of RidL is critical for
binding of the L. pneumophila effector to the Vps29 retromer subunit and displacement of the
regulator TBC1D5.
distinct Legionella-containing vacuole (LCV). LCV formation is a complex process that
involves a plethora of type IV-secreted effector proteins. The effector RidL binds the Vps29
retromer subunit, blocks retrograde vesicle trafficking, and promotes intracellular bacterial
replication. Here, we reveal that the 29-kDa N-terminal domain of RidL (RidL2–281) adopts a
“foot-like” fold comprising a protruding β-hairpin at its “heel”. The deletion of the β-hairpin,
the exchange to Glu of Ile170 in the β-hairpin, or Leu152 in Vps29 abolishes the interaction in
eukaryotic cells and in vitro. RidL2–281 or RidL displace the Rab7 GTPase-activating protein
(GAP) TBC1D5 from the retromer and LCVs, respectively, and TBC1D5 promotes the
intracellular growth of L. pneumophila. Thus, the hydrophobic β-hairpin of RidL is critical for
binding of the L. pneumophila effector to the Vps29 retromer subunit and displacement of the
regulator TBC1D5.
Date Issued
2017-11-16
Date Acceptance
2017-09-22
Citation
Nature Communications, 2017, 8
ISSN
2041-1723
Publisher
Nature Publishing Group
Journal / Book Title
Nature Communications
Volume
8
Copyright Statement
This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. The images or other third party
material in this article are included in the article’s Creative Commons license, unless
indicated otherwise in a credit line to the material. If material is not included in the
article’s Creative Commons license and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this license, visit http://creativecommons.org/
licenses/by/4.0/.
© The Author(s) 2017
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. The images or other third party
material in this article are included in the article’s Creative Commons license, unless
indicated otherwise in a credit line to the material. If material is not included in the
article’s Creative Commons license and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this license, visit http://creativecommons.org/
licenses/by/4.0/.
© The Author(s) 2017
Subjects
MD Multidisciplinary
Publication Status
Published
Article Number
1543