Dataset Information

Multiple Orientia tsutsugamushi ankyrin repeat proteins interact with SCF1 ubiquitin ligase complex and eukaryotic elongation factor 1 ?.

ABSTRACT:

Background

Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular bacterium. Previously, a large number of genes that encode proteins containing eukaryotic protein-protein interaction motifs such as ankyrin-repeat (Ank) domains were identified in the O. tsutsugamushi genome. However, little is known about the Ank protein function in O. tsutsugamushi.

Methodology/principal findings

To characterize the function of Ank proteins, we investigated a group of Ank proteins containing an F-box-like domain in the C-terminus in addition to the Ank domains. All nine selected ank genes were expressed at the transcriptional level in host cells infected with O. tsutsugamushi, and specific antibody responses against three Ank proteins were detected in the serum from human patients, indicating an active expression of the bacterial Ank proteins post infection. When ectopically expressed in HeLa cells, the Ank proteins of O. tsutsugamushi were consistently found in the nucleus and/or cytoplasm. In GST pull-down assays, multiple Ank proteins specifically interacted with Cullin1 and Skp1, core components of the SCF1 ubiquitin ligase complex, as well as the eukaryotic elongation factor 1 ? (EF1?). Moreover, one Ank protein co-localized with the identified host targets and induced downregulation of EF1? potentially via enhanced ubiquitination. The downregulation of EF1? was observed consistently in diverse host cell types infected with O. tsutsugamushi.

Conclusion/significance

These results suggest that conserved targeting and subsequent degradation of EF1? by multiple O. tsutsugamushi Ank proteins could be a novel bacterial strategy for replication and/or pathogenesis during mammalian host infection.

SUBMITTER: Min CK

PROVIDER: S-EPMC4148323 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Multiple Orientia tsutsugamushi ankyrin repeat proteins interact with SCF1 ubiquitin ligase complex and eukaryotic elongation factor 1 α.

Min Chan-Ki CK Kwon Ye-Jin YJ Ha Na-Young NY Cho Bon-A BA Kim Jo-Min JM Kwon Eun-Kyung EK Kim Yeon-Sook YS Choi Myung-Sik MS Kim Ik-Sang IS Cho Nam-Hyuk NH

PloS one 20140828 8

<h4>Background</h4>Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular bacterium. Previously, a large number of genes that encode proteins containing eukaryotic protein-protein interaction motifs such as ankyrin-repeat (Ank) domains were identified in the O. tsutsugamushi genome. However, little is known about the Ank protein function in O. tsutsugamushi.<h4>Methodology/principal findings</h4>To characterize the function of Ank proteins, we investigated a gr ...[more]

PMID: 25166298

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