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Title: Crystal Structure of Borrelia turicatae protein, BTA121, a differentially regulated  gene in the tick-mammalian transmission cycle of relapsing fever spirochetes

Abstract

Tick-borne relapsing fever (RF) borreliosis is a neglected disease that is often misdiagnosed. RF species circulating in the United States include Borrelia turicatae, which is transmitted by argasid ticks. Environmental adaptation by RF Borrelia is poorly understood, however our previous studies indicated differential regulation of B. turicatae genes localized on the 150 kb linear megaplasmid during the tick-mammalian transmission cycle, including bta121. This gene is up-regulated by B. turicatae in the tick versus the mammal, and the encoded protein (BTA121) is predicted to be surface localized. The structure of BTA121 was solved by single-wavelength anomalous dispersion (SAD) using selenomethionine-derivative protein. The topology of BTA121 is unique with four helical domains organized into two helical bundles. Due to the sequence similarity of several genes on the megaplasmid, BTA121 can serve as a model for their tertiary structures. BTA121 has large interconnected tunnels and cavities that can accommodate ligands, notably long parallel helices, which have a large hydrophobic central pocket. Preliminary in-vitro studies suggest that BTA121 binds lipids, notably palmitate with a similar order of binding affinity as tablysin-15, a known palmitate-binding protein. The reported data will guide mechanistic studies to determine the role of BTA121 in the tick-mammalian transmission cycle ofmore » B. turicatae.« less

Authors:
; ; ; ; ; ; ; ; ORCiD logo
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NCI
OSTI Identifier:
1409099
Resource Type:
Journal Article
Resource Relation:
Journal Name: Scientific Reports; Journal Volume: 7; Journal Issue: 1
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Luo, Zhipu, Kelleher, Alan J., Darwiche, Rabih, Hudspeth, Elissa M., Shittu, Oluwatosin K., Krishnavajhala, Aparna, Schneiter, Roger, Lopez, Job E., and Asojo, Oluwatoyin A. Crystal Structure of Borrelia turicatae protein, BTA121, a differentially regulated  gene in the tick-mammalian transmission cycle of relapsing fever spirochetes. United States: N. p., 2017. Web. doi:10.1038/s41598-017-14959-9.
Luo, Zhipu, Kelleher, Alan J., Darwiche, Rabih, Hudspeth, Elissa M., Shittu, Oluwatosin K., Krishnavajhala, Aparna, Schneiter, Roger, Lopez, Job E., & Asojo, Oluwatoyin A. Crystal Structure of Borrelia turicatae protein, BTA121, a differentially regulated  gene in the tick-mammalian transmission cycle of relapsing fever spirochetes. United States. doi:10.1038/s41598-017-14959-9.
Luo, Zhipu, Kelleher, Alan J., Darwiche, Rabih, Hudspeth, Elissa M., Shittu, Oluwatosin K., Krishnavajhala, Aparna, Schneiter, Roger, Lopez, Job E., and Asojo, Oluwatoyin A. Fri . "Crystal Structure of Borrelia turicatae protein, BTA121, a differentially regulated  gene in the tick-mammalian transmission cycle of relapsing fever spirochetes". United States. doi:10.1038/s41598-017-14959-9.
@article{osti_1409099,
title = {Crystal Structure of Borrelia turicatae protein, BTA121, a differentially regulated  gene in the tick-mammalian transmission cycle of relapsing fever spirochetes},
author = {Luo, Zhipu and Kelleher, Alan J. and Darwiche, Rabih and Hudspeth, Elissa M. and Shittu, Oluwatosin K. and Krishnavajhala, Aparna and Schneiter, Roger and Lopez, Job E. and Asojo, Oluwatoyin A.},
abstractNote = {Tick-borne relapsing fever (RF) borreliosis is a neglected disease that is often misdiagnosed. RF species circulating in the United States include Borrelia turicatae, which is transmitted by argasid ticks. Environmental adaptation by RF Borrelia is poorly understood, however our previous studies indicated differential regulation of B. turicatae genes localized on the 150 kb linear megaplasmid during the tick-mammalian transmission cycle, including bta121. This gene is up-regulated by B. turicatae in the tick versus the mammal, and the encoded protein (BTA121) is predicted to be surface localized. The structure of BTA121 was solved by single-wavelength anomalous dispersion (SAD) using selenomethionine-derivative protein. The topology of BTA121 is unique with four helical domains organized into two helical bundles. Due to the sequence similarity of several genes on the megaplasmid, BTA121 can serve as a model for their tertiary structures. BTA121 has large interconnected tunnels and cavities that can accommodate ligands, notably long parallel helices, which have a large hydrophobic central pocket. Preliminary in-vitro studies suggest that BTA121 binds lipids, notably palmitate with a similar order of binding affinity as tablysin-15, a known palmitate-binding protein. The reported data will guide mechanistic studies to determine the role of BTA121 in the tick-mammalian transmission cycle of B. turicatae.},
doi = {10.1038/s41598-017-14959-9},
journal = {Scientific Reports},
number = 1,
volume = 7,
place = {United States},
year = {Fri Nov 10 00:00:00 EST 2017},
month = {Fri Nov 10 00:00:00 EST 2017}
}
  • We have previously demonstrated that two salivary cysteine protease inhibitors from the Borrelia burgdorferi (Lyme disease) vector Ixodes scapularis - namely sialostatins L and L2 - play an important role in tick biology, as demonstrated by the fact that silencing of both sialostatins in tandem results in severe feeding defects. Here we show that sialostatin L2 - but not sialostatin L - facilitates the growth of B. burgdorferi in murine skin. To examine the structural basis underlying these differential effects of the two sialostatins, we have determined the crystal structures of both sialostatin L and L2. This is the firstmore » structural analysis of cystatins from an invertebrate source. Sialostatin L2 crystallizes as a monomer with an 'unusual' conformation of the N-terminus, while sialostatin L crystallizes as a domain-swapped dimer with an N-terminal conformation similar to other cystatins. Deletion of the 'unusual' N-terminal five residues of sialostatin L2 results in marked changes in its selectivity, suggesting that this region is a particularly important determinant of the biochemical activity of sialostatin L2. Collectively, our results reveal the structure of two tick salivary components that facilitate vector blood feeding and that one of them also supports pathogen transmission to the vertebrate host.« less
  • No abstract prepared.
  • The sterol carrier protein-2 like 3 gene (AeSCP-2L3), a new member of the SCP-2 protein family, is identified from the yellow fever mosquito, Aedes aegypti. The predicted molecular weight of AeSCP-2L3 is 13.4 kDa with a calculated pI of 4.98. AeSCP-2L3 transcription occurs in the larval feeding stages and the mRNA levels decrease in pupae and adults. The highest levels of AeSCP-2L3 gene expression are found in the body wall, and possibly originated in the fat body. This is the first report of a mosquito SCP-2-like protein with prominent expression in tissue other than the midgut. The X-ray protein crystalmore » structure of AeSCP-2L3 reveals a bound C16 fatty acid whose acyl tail penetrates deeply into a hydrophobic cavity. Interestingly, the ligand-binding cavity is slightly larger than previously described for AeSCP-2 (Dyer et al. J Biol Chem 278:39085-39091, 2003) and AeSCP-2L2 (Dyer et al. J Lipid Res M700460-JLR200, 2007). There are also an additional 10 amino acids in SCP-2L3 that are not present in other characterized mosquito SCP-2s forming an extended loop between {beta}3 and {beta}4. Otherwise, the protein backbone is exceedingly similar to other SCP-2 and SCP-2-like proteins. In contrast to this observed high structural homology of members in the mosquito SCP2 family, the amino acid sequence identity between the members is less than 30%. The results from structural analysis imply that there have been evolutionary constraints that favor the SCP-2 C{alpha} backbone fold while the specificity of ligand binding can be altered.« less
  • No abstract prepared.