{"id":{"repo_id":"nus","oai_identifier":"oai:scholarbank.nus.edu.sg:10635/231544"},"canonical_url":"https://search.dev.ndltd.org/etd/nus/oai:scholarbank.nus.edu.sg:10635/231544","repository":{"repo_id":"nus","name":"National University of Singapore","base_url":"https://scholarbank.nus.edu.sg/oai/request"},"display":{"title":"MOLECULAR MECHANISMS OF ATP-MODULATED LIQUID-LIQUID PHASE SEPARATION (LLPS) OF TDP-43 AND SARS-COV-2 NUCLEOCAPSID PROTEIN","abstract":"An estimated 40% of human proteome has undergone LLPS; delineating its molecular mechanisms may reveal principles undiscovered in physiology and open avenues for pathology. All living cells inexplicably maintain 2-14 mM ATP. Strikingly, in 2017, ATP (> 5 mM) was demonstrated to behave as a biohydrotrope to prevent protein LLPS. However, a high-resolution mechanism for ATP-modulated LLPS has been lacking so far. Here we included TDP-43 and SARS-CoV-2 N proteins as two paradigms to decipher how ATP regulates protein LLPS. The results revealed that ATP biphasically modulates the TDP-43 PLD and N protein LLPS by interacting with Arg/Lys and that ATP-modulated LLPS might be conserved from human to virus. These findings advance knowledge of ATP repertoire in fine-tuning LLPS and suggest ATP may be a crucial factor hijacked by SARS-CoV-2 to steer its life cycle. We, therefore, recommended ATP as a lead for designing drugs against neurodegeneration and viral infections.","abstract_html":"An estimated 40% of human proteome has undergone LLPS; delineating its molecular mechanisms may reveal principles undiscovered in physiology and open avenues for pathology. All living cells inexplicably maintain 2-14 mM ATP. Strikingly, in 2017, ATP (> 5 mM) was demonstrated to behave as a biohydrotrope to prevent protein LLPS. However, a high-resolution mechanism for ATP-modulated LLPS has been lacking so far. Here we included TDP-43 and SARS-CoV-2 N proteins as two paradigms to decipher how ATP regulates protein LLPS. The results revealed that ATP biphasically modulates the TDP-43 PLD and N protein LLPS by interacting with Arg/Lys and that ATP-modulated LLPS might be conserved from human to virus. These findings advance knowledge of ATP repertoire in fine-tuning LLPS and suggest ATP may be a crucial factor hijacked by SARS-CoV-2 to steer its life cycle. We, therefore, recommended ATP as a lead for designing drugs against neurodegeneration and viral infections.","abstract_has_math":false,"creators":["DANG MEI"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-04-13","date_published":"2022-04-13","updated_at":"2026-07-24T03:33:09Z","subjects":["Liquid-liquid phase separation (LLPS), ATP, nucleic acids, TDP-43 PLD, SARS-CoV-2 Nucleocapsid (N) protein, NMR spectroscopy"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["DANG MEI"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2022-04-13"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://scholarbank.nus.edu.sg/handle/10635/231544"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Liquid-liquid phase separation (LLPS), ATP, nucleic acids, TDP-43 PLD, SARS-CoV-2 Nucleocapsid (N) protein, NMR spectroscopy"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://scholarbank.nus.edu.sg/bitstreams/ae129267-4c39-49a0-9dcb-fc63be72a287/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["An estimated 40% of human proteome has undergone LLPS; delineating its molecular mechanisms may reveal principles undiscovered in physiology and open avenues for pathology. All living cells inexplicably maintain 2-14 mM ATP. Strikingly, in 2017, ATP (> 5 mM) was demonstrated to behave as a biohydrotrope to prevent protein LLPS. However, a high-resolution mechanism for ATP-modulated LLPS has been lacking so far. Here we included TDP-43 and SARS-CoV-2 N proteins as two paradigms to decipher how ATP regulates protein LLPS. The results revealed that ATP biphasically modulates the TDP-43 PLD and N protein LLPS by interacting with Arg/Lys and that ATP-modulated LLPS might be conserved from human to virus. These findings advance knowledge of ATP repertoire in fine-tuning LLPS and suggest ATP may be a crucial factor hijacked by SARS-CoV-2 to steer its life cycle. We, therefore, recommended ATP as a lead for designing drugs against neurodegeneration and viral infections."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["9310f40b2464828582f92ae562081eea","c98d5a810f726d35cb1fc53cd54dd992"]},{"key":"dc:title","label":"Title","values":["MOLECULAR MECHANISMS OF ATP-MODULATED LIQUID-LIQUID PHASE SEPARATION (LLPS) OF TDP-43 AND SARS-COV-2 NUCLEOCAPSID PROTEIN"]}]}],"canonical_facts":{"dc:creator":["DANG MEI"],"dc:date.issued":["2022-04-13"],"dc:description.abstract":["An estimated 40% of human proteome has undergone LLPS; delineating its molecular mechanisms may reveal principles undiscovered in physiology and open avenues for pathology. All living cells inexplicably maintain 2-14 mM ATP. Strikingly, in 2017, ATP (> 5 mM) was demonstrated to behave as a biohydrotrope to prevent protein LLPS. However, a high-resolution mechanism for ATP-modulated LLPS has been lacking so far. Here we included TDP-43 and SARS-CoV-2 N proteins as two paradigms to decipher how ATP regulates protein LLPS. The results revealed that ATP biphasically modulates the TDP-43 PLD and N protein LLPS by interacting with Arg/Lys and that ATP-modulated LLPS might be conserved from human to virus. These findings advance knowledge of ATP repertoire in fine-tuning LLPS and suggest ATP may be a crucial factor hijacked by SARS-CoV-2 to steer its life cycle. We, therefore, recommended ATP as a lead for designing drugs against neurodegeneration and viral infections."],"dc:format.checksum.md5":["9310f40b2464828582f92ae562081eea","c98d5a810f726d35cb1fc53cd54dd992"],"dc:identifier.uri":["https://scholarbank.nus.edu.sg/bitstreams/ae129267-4c39-49a0-9dcb-fc63be72a287/download"],"dc:relation.isreferencedby":["https://scholarbank.nus.edu.sg/handle/10635/231544"],"dc:subject":["Liquid-liquid phase separation (LLPS), ATP, nucleic acids, TDP-43 PLD, SARS-CoV-2 Nucleocapsid (N) protein, NMR spectroscopy"],"dc:title":["MOLECULAR MECHANISMS OF ATP-MODULATED LIQUID-LIQUID PHASE SEPARATION (LLPS) OF TDP-43 AND SARS-COV-2 NUCLEOCAPSID PROTEIN"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T03:33:09Z"}