Title |
Inhibition of eukaryotic translation by tetratricopeptide-repeat proteins of Orientia tsutsugamushi |
Author |
Sunyoung Bang1, Chan-Ki Min1,2, Na-Young Ha1,2, Myung-Sik Choi1, Ik-Sang Kim1, Yeon-Sook Kim3*, and Nam-Hyuk Cho1,2,4* |
Address |
1Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea, 2Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Republic of Korea, 3Divisions of Infectious Diseases, Chungnam National University Hospital, Daejeon 35015, Republic of Korea, 4Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul 35015, Republic of Korea |
Bibliography |
Journal of Microbiology, 54(2),136-144, 2016,
|
DOI |
10.1007/s12275-016-5599-5
|
Key Words |
Orientia tsutsugamushi, tetratricopeptide proteins,
DDX3, translation |
Abstract |
Orientia tsutsugamushi, an obligate intracellular bacterium, is
the causative agent of scrub typhus. The genome of Orientia
tsutsugamushi has revealed multiple ORFs encoding tetratricopeptide-
repeat (TPR) proteins. The TPR protein family
has been shown to be involved in a diverse spectrum of cellular
functions such as cell cycle control, transcription, protein
transport, and protein folding, especially in eukaryotic
cells. However, little is known about the function of the TPR
proteins in O. tsutsugamushi. To investigate the potential role
of TPR proteins in host-pathogen interaction, two oriential
TPR proteins were expressed in E. coli and applied for GSTpull
down assay. DDX3, a DEAD-box containing RNA helicase,
was identified as a specific eukaryotic target of the TPR
proteins. Since the RNA helicase is involved in multiple RNAmodifying
processes such as initiation of translation reaction,
we performed in vitro translation assay in the presence
of GST-TPR fusion proteins by using rabbit reticulocyte lysate
system. The TPR proteins inhibited in vitro translation
of a reporter luciferase in a dose dependent manner whereas
the GST control proteins did not. These results suggested TPR
proteins of O. tsutsugamushi might be involved in the modulation
of eukarytotic translation through the interaction with
DDX3 RNA helicase after secretion into host cytoplasm. |