{"id":{"repo_id":"queens","oai_identifier":"oai:queensu.scholaris.ca:1974/33460"},"canonical_url":"https://search.dev.ndltd.org/etd/queens/oai:queensu.scholaris.ca:1974/33460","repository":{"repo_id":"queens","name":"Queens University","base_url":"https://qspace.library.queensu.ca/server/oai/request"},"display":{"title":"Investigating the polyphosphate interactome with lysine- and histidine-rich proteins","abstract":"Inorganic polyphosphate (polyP) is a biomolecule whose diverse functionality greatly belies its simple structure. PolyP is comprised of repeated inorganic phosphate units forming high energy phosphoanhydride linked polymers. Numerous studies have highlighted its vast portfolio of functions that manifest their effects in a wide range of physiological pathways, including proteostasis, hemostasis, and phagocytosis. In particular, this thesis focuses on a remarkable post-translational modification (PTM)-like function of polyP, featured by its strong but non-covalent interaction with lysine repeat proteins, termed lysine polyphosphate modification (KPM). Amidst studying histidine polyphosphate modifications (HPM), proteins with repeating lysine residues emerged as plausible polyP targets. Screening within yeast, human, and bacterial proteomes revealed 19 novel KPM target proteins. Much like HPM, KPM exhibits polyP-dependent electrophoretic shifts on NuPAGE gels. However, upon deletion or mutation of the lysine residues the mobility shift is abolished indicating that these modifications are lysine-dependent. Additionally, KPM is also considered ionic in nature due to its susceptibility to both ionic strength and pH fluctuations. We show that polyP modifications can modulate protein activity of several enzymes, including the oncogenic GTPase, K-Ras, as well as the ATP-dependent RNA helicase, DDX55. We also studied the non-canonical HPM target protein, histidine-rich glycoprotein (HRG) to which we uncovered that HPM reduced its ability to bind IgG1. Moreover, we demonstrate that S100A9, a known ligand of HRG, is prone to multimerization in the presence of polyP. Though the physiological relevance of both HPM and KPM remain unclear, we suggest that the polyP-protein interactome is involved in widespread regulatory mechanisms of protein homeostasis and human health.","abstract_html":"Inorganic polyphosphate (polyP) is a biomolecule whose diverse functionality greatly belies its simple structure. PolyP is comprised of repeated inorganic phosphate units forming high energy phosphoanhydride linked polymers. Numerous studies have highlighted its vast portfolio of functions that manifest their effects in a wide range of physiological pathways, including proteostasis, hemostasis, and phagocytosis. In particular, this thesis focuses on a remarkable post-translational modification (PTM)-like function of polyP, featured by its strong but non-covalent interaction with lysine repeat proteins, termed lysine polyphosphate modification (KPM). Amidst studying histidine polyphosphate modifications (HPM), proteins with repeating lysine residues emerged as plausible polyP targets. Screening within yeast, human, and bacterial proteomes revealed 19 novel KPM target proteins. Much like HPM, KPM exhibits polyP-dependent electrophoretic shifts on NuPAGE gels. However, upon deletion or mutation of the lysine residues the mobility shift is abolished indicating that these modifications are lysine-dependent. Additionally, KPM is also considered ionic in nature due to its susceptibility to both ionic strength and pH fluctuations. We show that polyP modifications can modulate protein activity of several enzymes, including the oncogenic GTPase, K-Ras, as well as the ATP-dependent RNA helicase, DDX55. We also studied the non-canonical HPM target protein, histidine-rich glycoprotein (HRG) to which we uncovered that HPM reduced its ability to bind IgG1. Moreover, we demonstrate that S100A9, a known ligand of HRG, is prone to multimerization in the presence of polyP. Though the physiological relevance of both HPM and KPM remain unclear, we suggest that the polyP-protein interactome is involved in widespread regulatory mechanisms of protein homeostasis and human health.","abstract_has_math":false,"creators":["Lehotsky, Kirsten"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Biomedical and Molecular Sciences","school":null,"contributors":[],"advisors":["Jia, Zongchao"],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-09-24","date_published":"2024-09-24","updated_at":"2026-07-27T20:35:35Z","subjects":["histidine repeats","lysine repeats","polyphosphate","polyphosphate modification","HRG","K-Ras","DDX55","Pseudomonas aeruginosa","PASK"],"languages":["eng"],"rights":["Attribution 4.0 International"],"rights_urls":["http://creativecommons.org/licenses/by/4.0/"],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/1974/33460","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.department","label":"Department","values":["Biomedical and Molecular Sciences"]},{"key":"dc:contributor.supervisor","label":"Supervisor","values":["Jia, Zongchao"]},{"key":"dc:creator","label":"Author","values":["Lehotsky, Kirsten"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-09-24T12:50:10Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-09-24T12:50:10Z"]},{"key":"dc:date.issued","label":"Date","values":["2024-09-24"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["histidine repeats","lysine repeats","polyphosphate","polyphosphate modification","HRG","K-Ras","DDX55","Pseudomonas aeruginosa","PASK"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Attribution 4.0 International"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://creativecommons.org/licenses/by/4.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/1974/33460"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Inorganic polyphosphate (polyP) is a biomolecule whose diverse functionality greatly belies its simple structure. PolyP is comprised of repeated inorganic phosphate units forming high energy phosphoanhydride linked polymers. Numerous studies have highlighted its vast portfolio of functions that manifest their effects in a wide range of physiological pathways, including proteostasis, hemostasis, and phagocytosis. In particular, this thesis focuses on a remarkable post-translational modification (PTM)-like function of polyP, featured by its strong but non-covalent interaction with lysine repeat proteins, termed lysine polyphosphate modification (KPM). Amidst studying histidine polyphosphate modifications (HPM), proteins with repeating lysine residues emerged as plausible polyP targets. Screening within yeast, human, and bacterial proteomes revealed 19 novel KPM target proteins. Much like HPM, KPM exhibits polyP-dependent electrophoretic shifts on NuPAGE gels. However, upon deletion or mutation of the lysine residues the mobility shift is abolished indicating that these modifications are lysine-dependent. Additionally, KPM is also considered ionic in nature due to its susceptibility to both ionic strength and pH fluctuations. We show that polyP modifications can modulate protein activity of several enzymes, including the oncogenic GTPase, K-Ras, as well as the ATP-dependent RNA helicase, DDX55. We also studied the non-canonical HPM target protein, histidine-rich glycoprotein (HRG) to which we uncovered that HPM reduced its ability to bind IgG1. Moreover, we demonstrate that S100A9, a known ligand of HRG, is prone to multimerization in the presence of polyP. Though the physiological relevance of both HPM and KPM remain unclear, we suggest that the polyP-protein interactome is involved in widespread regulatory mechanisms of protein homeostasis and human health."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["M.Sc."]},{"key":"dc:title","label":"Title","values":["Investigating the polyphosphate interactome with lysine- and histidine-rich proteins"]}]}],"canonical_facts":{"dc:contributor.department":["Biomedical and Molecular Sciences"],"dc:contributor.supervisor":["Jia, Zongchao"],"dc:creator":["Lehotsky, Kirsten"],"dc:date.accessioned":["2024-09-24T12:50:10Z"],"dc:date.available":["2024-09-24T12:50:10Z"],"dc:date.issued":["2024-09-24"],"dc:description.abstract":["Inorganic polyphosphate (polyP) is a biomolecule whose diverse functionality greatly belies its simple structure. PolyP is comprised of repeated inorganic phosphate units forming high energy phosphoanhydride linked polymers. Numerous studies have highlighted its vast portfolio of functions that manifest their effects in a wide range of physiological pathways, including proteostasis, hemostasis, and phagocytosis. In particular, this thesis focuses on a remarkable post-translational modification (PTM)-like function of polyP, featured by its strong but non-covalent interaction with lysine repeat proteins, termed lysine polyphosphate modification (KPM). Amidst studying histidine polyphosphate modifications (HPM), proteins with repeating lysine residues emerged as plausible polyP targets. Screening within yeast, human, and bacterial proteomes revealed 19 novel KPM target proteins. Much like HPM, KPM exhibits polyP-dependent electrophoretic shifts on NuPAGE gels. However, upon deletion or mutation of the lysine residues the mobility shift is abolished indicating that these modifications are lysine-dependent. Additionally, KPM is also considered ionic in nature due to its susceptibility to both ionic strength and pH fluctuations. We show that polyP modifications can modulate protein activity of several enzymes, including the oncogenic GTPase, K-Ras, as well as the ATP-dependent RNA helicase, DDX55. We also studied the non-canonical HPM target protein, histidine-rich glycoprotein (HRG) to which we uncovered that HPM reduced its ability to bind IgG1. Moreover, we demonstrate that S100A9, a known ligand of HRG, is prone to multimerization in the presence of polyP. Though the physiological relevance of both HPM and KPM remain unclear, we suggest that the polyP-protein interactome is involved in widespread regulatory mechanisms of protein homeostasis and human health."],"dc:description.degree":["M.Sc."],"dc:identifier.uri":["https://hdl.handle.net/1974/33460"],"dc:language.iso":["eng"],"dc:rights":["Attribution 4.0 International"],"dc:rights.uri":["http://creativecommons.org/licenses/by/4.0/"],"dc:subject":["histidine repeats","lysine repeats","polyphosphate","polyphosphate modification","HRG","K-Ras","DDX55","Pseudomonas aeruginosa","PASK"],"dc:title":["Investigating the polyphosphate interactome with lysine- and histidine-rich proteins"],"dc:type":["thesis"]},"updated_at":"2026-07-27T20:35:35Z"}