Publication: Extended loop region of Hcp1 is critical for the assembly and function of type VI secretion system in Burkholderia pseudomallei.
Accepted Date
2015-01-13
Issued Date
2015-02-04
Copyright Date
2015
Resource Type
Language
eng
ISSN
2045-2322 (electronic)
Rights Holder(s)
Scientific reports
Bibliographic Citation
Lim YT, Jobichen C, Wong J, Limmathurotsakul D, Li S, Chen Y. et al. Extended loop region of Hcp1 is critical for the assembly and function of type VI secretion system in Burkholderia pseudomallei. Sci Rep. 2015 Feb 4;5:8235.
Suggested Citation
Lim, Yan Ting, Jobichen, Chacko, Wong, Jocelyn, Direk Limmathurotsakul, ดิเรก ลิ้มมธุรสกุล, Li, Shaowei, Chen, Yahua, Raida, Manfred, Nalini Srinivasan, MacAry, Paul Anthony, Sivaraman, J., Gan, Yunn-Hwen Extended loop region of Hcp1 is critical for the assembly and function of type VI secretion system in Burkholderia pseudomallei.. Lim YT, Jobichen C, Wong J, Limmathurotsakul D, Li S, Chen Y. et al. Extended loop region of Hcp1 is critical for the assembly and function of type VI secretion system in Burkholderia pseudomallei. Sci Rep. 2015 Feb 4;5:8235.. doi:10.1038/srep08235. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/845
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Title
Extended loop region of Hcp1 is critical for the assembly and function of type VI secretion system in Burkholderia pseudomallei.
Corresponding Author(s)
Abstract
The Type VI Secretion System cluster 1 (T6SS1) is essential for the pathogenesis
of Burkholderia pseudomallei, the causative agent of melioidosis, a disease
endemic in the tropics. Inside host cells, B. pseudomallei escapes into the
cytosol and through T6SS1, induces multinucleated giant cell (MNGC) formation
that is thought to be important for bacterial cell to cell spread. The
hemolysin-coregulated protein (Hcp) is both a T6SS substrate, as well as
postulated to form part of the T6SS secretion tube. Our structural study reveals
that Hcp1 forms hexameric rings similar to the other Hcp homologs but has an
extended loop (Asp40-Arg56) that deviates significantly in position compared to
other Hcp structures and may act as a key contact point between adjacent
hexameric rings. When two residues within the loop were mutated, the mutant
proteins were unable to stack as dodecamers, suggesting defective tube assembly.
Moreover, infection with a bacterial mutant containing in situ substitution of
these hcp1 residues abolishes Hcp1 secretion inside infected cells and MNGC
formation. We further show that Hcp has the ability to preferentially bind to the
surface of antigen-presenting cells, which may contribute to its immunogenicity
in inducing high titers of antibodies seen in melioidosis patients.