Amino Acid and Structural Variability of Yersinia Pestis LcrV Protein

Infect Genet Evol. 2010 Jan;10(1):137-45. doi: 10.1016/j.meegid.2009.10.003. Epub 2009 Oct 14.

Abstract

The LcrV protein is a multifunctional virulence factor and protective antigen of the plague bacterium and is generally conserved between the epidemic strains of Yersinia pestis. We investigated the diversity in the LcrV sequences among non-epidemic Y. pestis strains which have a limited virulence in selected animal models and for humans. Sequencing of lcrV genes from 19 Y. pestis strains belonging to different phylogenetic groups (subspecies) showed that the LcrV proteins possess four major variable hotspots at positions 18, 72, 273, and 324-326. These major variations, together with other minor substitutions in amino acid sequences, allowed us to classify the LcrV alleles into five sequence types (A-E). We observed that the strains of different Y. pestis "subspecies" can have the same type of LcrV, including that conserved in epidemic strains, and different types of LcrV can exist within the same natural plague focus. Therefore, the phenomenon of "selective virulence" characteristic of the strains of the microtus biovar is unlikely to be the result of polymorphism of the V antigen. The LcrV polymorphisms were structurally analyzed by comparing the modeled structures of LcrV from all available strains. All changes except one occurred either in flexible regions or on the surface of the protein, but local chemical properties (i.e. those of a hydrophobic, hydrophilic, amphipathic, or charged nature) were conserved across all of the strains. Polymorphisms in flexible and surface regions are likely subject to less selective pressure, and have a limited impact on the structure. In contrast, the substitution of tryptophan at position 113 with either glutamic acid or glycine likely has a serious influence on the regional structure of the protein, and these mutations might have an effect on the function of LcrV. The polymorphisms at positions 18, 72 and 273 were accountable for differences in the oligomerization of LcrV.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Amino Acids / genetics*
  • Antigens, Bacterial / chemistry*
  • Antigens, Bacterial / genetics*
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / immunology
  • Genes, Bacterial
  • Lysine / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Pore Forming Cytotoxic Proteins / chemistry*
  • Pore Forming Cytotoxic Proteins / genetics*
  • Sequence Homology, Amino Acid
  • Virulence Factors / genetics
  • Virulence Factors / immunology
  • Virulence Factors / metabolism
  • Yersinia pestis / genetics*
  • Yersinia pestis / immunology
  • Yersinia pestis / pathogenicity

Substances

  • Amino Acids
  • Antigens, Bacterial
  • Bacterial Proteins
  • LcrV protein, Yersinia
  • Pore Forming Cytotoxic Proteins
  • Virulence Factors
  • Lysine