Multiple Pleomorphic Tetramers of Thermostable Direct Hemolysin from Grimontia hollisae in Exerting Hemolysis and Membrane Binding

Sci Rep. 2019 Jul 8;9(1):9833. doi: 10.1038/s41598-019-46354-x.

Abstract

Oligomerization of protein into specific quaternary structures plays important biological functions, including regulation of gene expression, enzymes activity, and cell-cell interactions. Here, we report the determination of two crystal structures of the Grimontia hollisae (formally described as Vibrio hollisae) thermostable direct hemolysin (Gh-TDH), a pore-forming toxin. The toxin crystalized in the same space group of P21212, but with two different crystal packing patterns, each revealing three consistent tetrameric oligomerization forms called Oligomer-I, -II, and -III. A central pore with comparable depth of ~50 Å but differing in shape and size was observed in all determined toxin tetrameric oligomers. A common motif of a toxin dimer was found in all determined structures, suggesting a plausible minimum functional unit within the tetrameric structure in cell membrane binding and possible hemolytic activity. Our results show that bacterial toxins may form a single or highly symmetric oligomerization state when exerting their biological functions. The dynamic nature of multiple symmetric oligomers formed upon release of the toxin may open a niche for bacteria survival in harsh living environments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism
  • Cell Membrane / metabolism*
  • Crystallography, X-Ray
  • HeLa Cells
  • Hemolysin Proteins / chemistry*
  • Hemolysin Proteins / genetics
  • Hemolysin Proteins / metabolism*
  • Hemolysis
  • Humans
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Rabbits
  • Vibrionaceae / chemistry
  • Vibrionaceae / genetics
  • Vibrionaceae / metabolism*

Substances

  • Bacterial Proteins
  • Bacterial Toxins
  • Hemolysin Proteins
  • thermostable direct hemolysin

Supplementary concepts

  • Grimontia hollisae