Distribution and Evolution of Yersinia Leucine-Rich Repeat Proteins

Abstract

c Leucine-rich repeat (LRR) proteins are widely distributed in bacteria, playing important roles in various protein-protein interaction processes. In Yersinia, the well-characterized type III secreted effector YopM also belongs to the LRR protein family and is encoded by virulence plasmids. However, little has been known about other LRR members encoded by Yersinia genomes or their evolution. In this study, the Yersinia LRR proteins were comprehensively screened, categorized, and compared. The LRR proteins encoded by chromosomes (LRR1 proteins) appeared to be more similar to each other and different from those encoded by plasmids (LRR2 proteins) with regard to repeat-unit length, amino acid composition profile, and gene expression regulation circuits. LRR1 proteins were also different from LRR2 proteins in that the LRR1 proteins contained an E3 ligase domain (NEL domain) in the C-terminal region or an NEL domain-encoding nucleotide relic in flanking genomic sequences. The LRR1 proteinencoding genes (LRR1 genes) varied dramatically and were categorized into 4 subgroups (a to d), with the LRR1a to -c genes evolving from the same ancestor and LRR1d genes evolving from another ancestor. The consensus and ancestor repeat-unit sequences were inferred for different LRR1 protein subgroups by use of a maximum parsimony modeling strategy. Structural modeling disclosed very similar repeat-unit structures between LRR1 and LRR2 proteins despite the different unit lengths and amino acid compositions. Structural constraints may serve as the driving force to explain the observed mutations in the LRR regions. This study suggests that there may be functional variation and lays the foundation for future experiments investigating the functions of the chromosomally encoded LRR proteins of Yersinia.

DNA sequence repeats identify numerous Type I restriction‐modification systems that are potential epigenetic regulators controlling phase‐variable regulons; phasevarions

“…(poly C tracts) and Mycoplasmataceae (dinucleotide tracts) are represented, which is not surprising given the prevalence of these types of repeats in these organisms, 49 with many R-M systems in Mycoplasmas previously identified as containing SSRs. However, the resulting amino acid repeats they encode may have important functional implications, as seen with other amino acid repeat containing proteins such as the RTX family of toxins produced by Gram-negative bacteria, 54 Leucine Rich Repeat (LRP) proteins, 55,56 and HsdS proteins. 52 We also identify a number of phase-variable hsdR genes in unusual or emerging pathogens such as EleORF768 from Eggerthella lenta, an anaerobic Gram-positive bacilli associated with abdominal sepsis, and Slu143ORF9045 from Staphylococcus lugdunensis, a member of the Staphylococci that has been known to cause septic arthritis.…”

A global survey of bacterial type III secretion systems and their effectors

“…This has prompted the development of effector prediction algorithms that focus on shared features of T3SEs, which includes amino acid biases that characterize the secretion and translocation signal (Arnold et al, 2009;Samudrala et al, 2009;Wang et al, 2011). Despite this, homology remains an effective way to catalog existing T3SE diversity, and to find potentially new distantly homologous effectors in newly sequenced genomes (Hu et al, 2016). As T3SEs are categorized, families delimited and T3SE distribution established, combinatorial T3SE prediction strategies can be developed that amalgamate sequence similarity as well as the associations of particular T3SEs with specific T3SSs.…”

The Evolution and Sequence Diversity of FhuA inSalmonellaandEscherichia

“…Selection pressures based on bacteriophage binding have been observed in the past (34,35) and we hypothesize that evolved resistance to key bacteriophages could be responsible for some of the group-specific changes in surface-exposed FhuA loops. We recently found that Yersinia leucine-rich repeat genes had frequent mutations that were constrained to maintain protein activity and overall structure (36). Instead of random nucleotide substitutions, the amino acid codons tended to mutate with maximum parsimony (i.e., in the most straightforward and simplest way).…”

“…Instead of random nucleotide substitutions, the amino acid codons tended to mutate with maximum parsimony (i.e., in the most straightforward and simplest way). Therefore, the observed mutations at the peptide level often showed predictable patterns rather than total irregularity (36).…”

“…It is possible for a protein to have multiple activities, some of which may be conserved and essential for organism survival, and therefore under negative selection, while others could be placed under positive selection. Such proteins could adopt co-mutations at multiple loci to simultaneously change some function, such as alteration of a ligand-recognition motif, while still maintaining the essential activity (36). Under these two hypotheses, the mosaic evolution patterns, the mutation loci and the possible protein activities of FhuA could be well explained and associated.…”