3WX6

Crystal structure of Type Six Secretion System protein

Summary for 3WX6

• Entry DOI: 10.2210/pdb3wx6/pdb
• Descriptor: Uncharacterized protein (2 entities in total)
• Functional Keywords: hexameric assembly, hexameric ring, t6ss protein, unknown function
• Biological source: Burkholderia pseudomallei K96243
• Total number of polymer chains: 2
• Total formula weight: 38093.21

Authors

Jobichen, C.,Sivaraman, J. (deposition date: 2014-07-17, release date: 2015-03-04)

Primary 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.
Extended Loop Region of Hcp1 is Critical for the Assembly and Function of Type VI Secretion System in Burkholderia pseudomallei.
Sci Rep, 5:8235-8235, 2015

PubMed 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.

PubMed: 25648885
DOI: 10.1038/srep08235

Experimental method

X-RAY DIFFRACTION (2.7 Å)