Structure analysis of the telomere resolvase from the Lyme disease spirochete Borrelia garinii reveals functional divergence of its C-terminal domain

Semper, Cameron; Watanabe, Nobuhiko; Karimullina, Elina; Patel, Deepak T.; Leo, Rosa Di; Castellanos, Mildred; Patel, Dhruvin H.; Chaconas, George; Savchenko, Alexei

doi:10.1093/nar/gkae580

Structure analysis of the telomere resolvase from the Lyme disease spirochete Borrelia garinii reveals functional divergence of its C-terminal domain

Journal Article · Tue Jul 09 00:00:00 EDT 2024 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkae580· OSTI ID:2471056

^[1]; Watanabe, Nobuhiko ^[1]; Karimullina, Elina ^[1]; Patel, Deepak T. ^[1]; Leo, Rosa Di ^[2]; Castellanos, Mildred ^[1]; ^[1]; Chaconas, George ^[1]; ^[3]

University of Calgary, AB (Canada)
University of Toronto, ON (Canada)
University of Calgary, AB (Canada); University of Toronto, ON (Canada)

Borrelia spirochetes are the causative agents of Lyme disease and relapsing fever, two of the most common tick-borne illnesses. A characteristic feature of these spirochetes is their highly segmented genomes which consists of a linear chromosome and a mixture of up to approximately 24 linear and circular extrachromosomal plasmids. The complexity of this genomic arrangement requires multiple strategies for efficient replication and partitioning during cell division, including the generation of hairpin ends found on linear replicons mediated by the essential enzyme ResT, a telomere resolvase. Using an integrative structural biology approach employing advanced modelling, circular dichroism, X-ray crystallography and small-angle X-ray scattering, we have generated high resolution structural data on ResT from B. garinii. Our data provides the first high-resolution structures of ResT from Borrelia spirochetes and revealed active site positioning in the catalytic domain. We also demonstrate that the C-terminal domain of ResT is required for both transesterification steps of telomere resolution, and is a requirement for DNA binding, distinguishing ResT from other telomere resolvases from phage and bacteria. These results advance our understanding of the molecular function of this essential enzyme involved in genome maintenance in Borrelia pathogens.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)

Sponsoring Organization:: Department of Health and Human Services; National Institute of Allergy and Infectious Diseases; National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2471056

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 14 Vol. 52; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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Structure analysis of the telomere resolvase from the Lyme disease spirochete Borrelia garinii reveals functional divergence of its C-terminal domain

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