8Z7K

Crystal structure of Hemolysin co-regulated protein 1 (Hcp1) VariantB from Burkholderia pseudomallei

Summary for 8Z7K

• Entry DOI: 10.2210/pdb8z7k/pdb
• Descriptor: Hcp family type VI secretion system effector, SULFATE ION (3 entities in total)
• Functional Keywords: burkholderia pseudomallei, melioidosis, hemolysin co-regulated protein (hcp1), protein transport
• Biological source: Burkholderia pseudomallei
• Total number of polymer chains: 2
• Total formula weight: 40023.05

Authors

Lebedev, A.A.,Charoenwattanasatien, R.,Tandhavanant, S.,Chantratita, N. (deposition date: 2024-04-20, release date: 2024-12-25, Last modification date: 2025-01-22)

Primary citation

Tandhavanant, S.,Yimthin, T.,Sengyee, S.,Charoenwattanasatien, R.,Lebedev, A.A.,Lafontaine, E.R.,Hogan, R.J.,Chewapreecha, C.,West, T.E.,Brett, P.J.,Burtnick, M.N.,Chantratita, N.
Genetic variation of hemolysin co-regulated protein 1 affects the immunogenicity and pathogenicity of Burkholderia pseudomallei.
Plos Negl Trop Dis, 19:e0012758-e0012758, 2025

PubMed Abstract: Hemolysin co-regulated protein 1 (Hcp1) is a component of the cluster 1 Type VI secretion system (T6SS1) that plays a key role during the intracellular lifecycle of Burkholderia pseudomallei. Hcp1 is recognized as a promising target antigen for developing melioidosis diagnostics and vaccines. While the gene encoding Hcp1 is retained across B. pseudomallei strains, variants of hcp1 have recently been identified. This study aimed to examine the prevalence of hcp1 variants in clinical isolates of B. pseudomallei, assess the antigenicity of the Hcp1 variants, and the ability of strains expressing these variants to stimulate multinucleated giant cell (MNGC) formation in comparison to strains expressing wild-type Hcp1 (Hcp1wt). Sequence analysis of 1,283 primary clinical isolates of B. pseudomallei demonstrated the presence of 8 hcp1 alleles encoding three types of Hcp1 proteins, including Hcp1wt (98.05%), Hcp1variant A (1.87%) and Hcp1variant B (0.08%). Compared to strains expressing Hcp1wt, those expressing the dominant variant, Hcp1variant A, stimulated lower levels of Hcp1variant A-specific antibody responses in melioidosis patients. Interestingly, when Hcp1variant A was expressed in B. pseudomallei K96243, this strain retained the ability to stimulate MNGC formation in A549 cells. In contrast, however, similar experiments with the Hcp1variant B demonstrated a decreased ability of B. pseudomallei to stimulate MNGC formation. Collectively, these results show that B. pseudomallei strains expressing variants of Hcp1 elicit variable antibody responses in melioidosis patients and differ in their ability to promote MNGC formation in cell culture.

PubMed: 39761280
DOI: 10.1371/journal.pntd.0012758

Experimental method

X-RAY DIFFRACTION (1.582 Å)