Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep08235
Title: Extended loop region of Hcp1 is critical for the assembly and function of type VI secretion system in Burkholderia pseudomallei
Authors: Lim, Y.T 
Jobichen, C 
Wong, J 
Limmathurotsakul, D
Li, S
Chen, Y 
Raida, M 
Srinivasan, N
Macary, P.A 
Sivaraman, J 
Gan, Y.-H 
Keywords: bacterium antibody
outer membrane protein
protein binding
recombinant protein
type VI secretion system
amino acid sequence
animal
antigen presenting cell
Burkholderia pseudomallei
cell line
chemical structure
chemistry
genetics
human
immunology
macrophage
melioidosis
metabolism
microbiology
molecular genetics
mouse
mutation
physiology
protein conformation
protein domain
protein multimerization
type VI secretion system
Amino Acid Sequence
Animals
Antibodies, Bacterial
Antigen-Presenting Cells
Bacterial Outer Membrane Proteins
Burkholderia pseudomallei
Cell Line
Humans
Macrophages
Melioidosis
Mice
Models, Molecular
Molecular Sequence Data
Mutation
Protein Binding
Protein Conformation
Protein Interaction Domains and Motifs
Protein Multimerization
Recombinant Proteins
Type VI Secretion Systems
Issue Date: 2015
Citation: Lim, Y.T, Jobichen, C, Wong, J, Limmathurotsakul, D, Li, S, Chen, Y, Raida, M, Srinivasan, N, Macary, P.A, Sivaraman, J, Gan, Y.-H (2015). Extended loop region of Hcp1 is critical for the assembly and function of type VI secretion system in Burkholderia pseudomallei. Scientific Reports 5 : 8235. ScholarBank@NUS Repository. https://doi.org/10.1038/srep08235
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. pseudomalleiescapes 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 situsubstitution of these hcp1residues 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.
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/175999
ISSN: 2045-2322
DOI: 10.1038/srep08235
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1038_srep08235.pdf2.72 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

21
checked on Mar 3, 2021

Page view(s)

51
checked on Mar 5, 2021

Download(s)

1
checked on Mar 5, 2021

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.