Structure of the Borrelia burgdorferi ATP-dependent metalloprotease FtsH in its functionally relevant hexameric form

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dc.contributor.authorBrangulis, Kalvis
dc.contributor.authorDrunka, Laura
dc.contributor.authorAkopjana, Inara
dc.contributor.authorTars, Kaspars
dc.contributor.institutionDepartment of Human Physiology and Biochemistry
dc.date.accessioned2023-10-28T19:35:03Z
dc.date.available2023-10-28T19:35:03Z
dc.date.issued2024-01
dc.descriptionPublisher Copyright: © 2023 The Authors
dc.description.abstractATP-dependent proteases FtsH are conserved in bacteria, mitochondria, and chloroplasts, where they play an essential role in degradation of misfolded/unneeded membrane and cytosolic proteins. It has also been demonstrated that the FtsH homologous protein BB0789 is crucial for mouse and tick infectivity and in vitro growth of the Lyme disease-causing agent Borrelia burgdorferi. This is not surprising, considering B. burgdorferi complex life cycle, residing in both in mammals and ticks, which requires a wide range of membrane proteins and short-lived cytosolic regulatory proteins to invade and persist in the host organism. In the current study, we have solved the crystal structure of the cytosolic BB0789 166 - 614, lacking both N-terminal transmembrane α-helices and the small periplasmic domain. The structure revealed the arrangement of the AAA+ ATPase and the zinc-dependent metalloprotease domains in a hexamer ring, which is essential for ATPase and proteolytic activity. The AAA+ domain was found in an ADP-bound state, while the protease domain showed coordination of a zinc ion by two histidine residues and one aspartic acid residue. The loop region that forms the central pore in the oligomer was poorly defined in the crystal structure and therefore predicted by AlphaFold to complement the missing structural details, providing a complete picture of the functionally relevant hexameric form of BB0789. We confirmed that BB0789 is functionally active, possessing both protease and ATPase activities, thus providing novel structural-functional insights into the protein, which is known to be absolutely necessary for B. burgdorferi to survive and cause Lyme disease.en
dc.description.statusPeer reviewed
dc.format.extent8
dc.format.extent10978115
dc.identifier.citationBrangulis, K, Drunka, L, Akopjana, I & Tars, K 2024, 'Structure of the Borrelia burgdorferi ATP-dependent metalloprotease FtsH in its functionally relevant hexameric form', Biochimica et Biophysica Acta - Proteins and Proteomics, vol. 1872, no. 1, 140969, pp. 1-8. https://doi.org/10.1016/j.bbapap.2023.140969
dc.identifier.doi10.1016/j.bbapap.2023.140969
dc.identifier.issn1570-9639
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/14924
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85174469018&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofBiochimica et Biophysica Acta - Proteins and Proteomics
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectLyme borreliosis
dc.subjectMetalloenzyme
dc.subjectAAA+ protease
dc.subjectSpirochetes
dc.subjectX-ray crystallography
dc.subject1.6 Biological sciences
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.titleStructure of the Borrelia burgdorferi ATP-dependent metalloprotease FtsH in its functionally relevant hexameric formen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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