TY - JOUR
T1 - Amino acid and structural variability of Yersinia pestis LcrV protein
AU - Anisimov, Andrey P.
AU - Dentovskaya, Svetlana V.
AU - Panfertsev, Evgeniy A.
AU - Svetoch, Tat'yana E.
AU - Kopylov, Pavel Kh
AU - Segelke, Brent W.
AU - Zemla, Adam
AU - Telepnev, Maxim V.
AU - Motin, Vladimir L.
N1 - Funding Information:
This work was supported by the International Science and Technology Center (project #2426), Russian Foundation for Basic Research (project 08-04-00405-a), Sealy Center for Vaccine Development of the University of Texas Medical Branch at Galveston, and the NIH/NIAID grant 1R43 AI71634-01A2 . This work was implemented under the auspices of the U.S. Department of Energy under contract no. W-7405-Eng-48.
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
KW - 3D structure
KW - LcrV
KW - Modeling
KW - Oligomerization
KW - Polymorphism
KW - Yersinia pestis
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U2 - 10.1016/j.meegid.2009.10.003
DO - 10.1016/j.meegid.2009.10.003
M3 - Article
C2 - 19835996
AN - SCOPUS:72449129442
SN - 1567-1348
VL - 10
SP - 137
EP - 145
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
IS - 1
ER -