{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/45293"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/45293","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Molecular mechanisms of gating and selectivity in transport channels","abstract":"Transport channels and pores are of fundamental importance for translocation of molecules across the otherwise-impermeable biological membrane. As a conduit for the passage of material, specific membrane channels must accomplish the task of selective transport of molecules, while preventing unnecessary loss of other cellular material. The nuclear pore complex (NPC), and the mechanosensitive channel of small conductance, MscS are the focus of the research presented in this thesis. NPCs are sole gateways for passage of material across the nuclear envelope of eukaryotic cells. Several unstructured proteins that are rich in phenylaline- glycine motifs (FG-nups) form the central transport channel. Small molecules passively diffuse through the channel but, larger molecules are selectively transported via transport factors (TFs), which apparently interact with the FG-repeats of the nups in the channel. To understand how nups are assembled in the interior of the NPC, assemblies of one kind of nup, starting from different initial states, are investigated. Results suggest nups form different structures in different regions of the central channel. While only molecules of size < 9nm can penetrate through, a limit known for passive diffusion, the resulting structure posed a selectivity barrier for larger molecules that can be penetrated only via TF interactions. Mechanosensitive (MS) channels, bacterial inner-membrane proteins, open and close in response to mechanical stimuli such as changes in membrane tension during osmotic stress. These channels act as safety valves preventing cell lysis upon hypoosmotic cell swelling: the channels open under membrane tension to release osmolytes along with water. MscS, consists, beside the transmembrane channel, of a large cytoplasmic domain (CD) that features a balloon-like, water filled chamber opening to the cytoplasm through seven side pores and a small distal pore. The CD is apparently a molecular sieve covering the channel, that optimizes loss of osmolytes during osmoadaptation. Diffusion theory and MD simulations are employed to explore the transport kinetics of Glu- and K+ as representative osmolytes. A role of a filter is suggested for the CD such that it balances passage of Glu- and K+ osmolytes, to yield a largely neutral efflux, thereby, reducing cell depolarization in the open state that also conserves to a large degree the essential metabolite Glu-.","abstract_html":"Transport channels and pores are of fundamental importance for translocation of molecules across the otherwise-impermeable biological membrane. As a conduit for the passage of material, specific membrane channels must accomplish the task of selective transport of molecules, while preventing unnecessary loss of other cellular material. The nuclear pore complex (NPC), and the mechanosensitive channel of small conductance, MscS are the focus of the research presented in this thesis. NPCs are sole gateways for passage of material across the nuclear envelope of eukaryotic cells. Several unstructured proteins that are rich in phenylaline- glycine motifs (FG-nups) form the central transport channel. Small molecules passively diffuse through the channel but, larger molecules are selectively transported via transport factors (TFs), which apparently interact with the FG-repeats of the nups in the channel. To understand how nups are assembled in the interior of the NPC, assemblies of one kind of nup, starting from different initial states, are investigated. Results suggest nups form different structures in different regions of the central channel. While only molecules of size &lt; 9nm can penetrate through, a limit known for passive diffusion, the resulting structure posed a selectivity barrier for larger molecules that can be penetrated only via TF interactions. Mechanosensitive (MS) channels, bacterial inner-membrane proteins, open and close in response to mechanical stimuli such as changes in membrane tension during osmotic stress. These channels act as safety valves preventing cell lysis upon hypoosmotic cell swelling: the channels open under membrane tension to release osmolytes along with water. MscS, consists, beside the transmembrane channel, of a large cytoplasmic domain (CD) that features a balloon-like, water filled chamber opening to the cytoplasm through seven side pores and a small distal pore. The CD is apparently a molecular sieve covering the channel, that optimizes loss of osmolytes during osmoadaptation. Diffusion theory and MD simulations are employed to explore the transport kinetics of Glu- and K+ as representative osmolytes. A role of a filter is suggested for the CD such that it balances passage of Glu- and K+ osmolytes, to yield a largely neutral efflux, thereby, reducing cell depolarization in the open state that also conserves to a large degree the essential metabolite Glu-.","abstract_has_math":false,"creators":["Gamini, Ramya Bhargavi"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biophysics & Computnl Biology","degree_department":null,"school":null,"contributors":["Schulten, Klaus J.","Tajkhorshid, Emad","Grosman, Claudio F."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-08-22T16:35:05Z","date_published":"2013-08-22T16:35:05Z","updated_at":"2026-07-22T22:25:34Z","subjects":["Transport Channels","Molecular Dynamics","nuclear pore complex","mechanosensitive channel of small conductance"],"languages":["en"],"rights":["Copyright 2013 Ramya Bhargavi Gamini"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/45293","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Schulten, Klaus J.","Tajkhorshid, Emad","Grosman, Claudio F."]},{"key":"dc:creator","label":"Author","values":["Gamini, Ramya Bhargavi"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2013-08-22T16:35:05Z","2013-08"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biophysics & Computnl Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Transport Channels","Molecular Dynamics","nuclear pore complex","mechanosensitive channel of small conductance"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2013 Ramya Bhargavi Gamini"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/45293"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Transport channels and pores are of fundamental importance for translocation of molecules across the otherwise-impermeable biological membrane. As a conduit for the passage of material, specific membrane channels must accomplish the task of selective transport of molecules, while preventing unnecessary loss of other cellular material. The nuclear pore complex (NPC), and the mechanosensitive channel of small conductance, MscS are the focus of the research presented in this thesis. NPCs are sole gateways for passage of material across the nuclear envelope of eukaryotic cells. Several unstructured proteins that are rich in phenylaline- glycine motifs (FG-nups) form the central transport channel. Small molecules passively diffuse through the channel but, larger molecules are selectively transported via transport factors (TFs), which apparently interact with the FG-repeats of the nups in the channel. To understand how nups are assembled in the interior of the NPC, assemblies of one kind of nup, starting from different initial states, are investigated. Results suggest nups form different structures in different regions of the central channel. While only molecules of size < 9nm can penetrate through, a limit known for passive diffusion, the resulting structure posed a selectivity barrier for larger molecules that can be penetrated only via TF interactions. Mechanosensitive (MS) channels, bacterial inner-membrane proteins, open and close in response to mechanical stimuli such as changes in membrane tension during osmotic stress. These channels act as safety valves preventing cell lysis upon hypoosmotic cell swelling: the channels open under membrane tension to release osmolytes along with water. MscS, consists, beside the transmembrane channel, of a large cytoplasmic domain (CD) that features a balloon-like, water filled chamber opening to the cytoplasm through seven side pores and a small distal pore. The CD is apparently a molecular sieve covering the channel, that optimizes loss of osmolytes during osmoadaptation. Diffusion theory and MD simulations are employed to explore the transport kinetics of Glu- and K+ as representative osmolytes. A role of a filter is suggested for the CD such that it balances passage of Glu- and K+ osmolytes, to yield a largely neutral efflux, thereby, reducing cell depolarization in the open state that also conserves to a large degree the essential metabolite Glu-.","Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2013-07-03T16:07:14Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 2 Gamini_Ramya.pdf: 49329612 bytes, checksum: 5ac9556bef87ad0add1fc21ae729f766 (MD5) Gamini_Ramya.pdf: 49345598 bytes, checksum: 2368eb9815f0987f487bd25ee903213f (MD5)","Made available in DSpace on 2013-08-22T16:35:05Z (GMT). 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NPCs are sole gateways for passage of material across the nuclear envelope of eukaryotic cells. Several unstructured proteins that are rich in phenylaline- glycine motifs (FG-nups) form the central transport channel. Small molecules passively diffuse through the channel but, larger molecules are selectively transported via transport factors (TFs), which apparently interact with the FG-repeats of the nups in the channel. To understand how nups are assembled in the interior of the NPC, assemblies of one kind of nup, starting from different initial states, are investigated. Results suggest nups form different structures in different regions of the central channel. While only molecules of size < 9nm can penetrate through, a limit known for passive diffusion, the resulting structure posed a selectivity barrier for larger molecules that can be penetrated only via TF interactions. Mechanosensitive (MS) channels, bacterial inner-membrane proteins, open and close in response to mechanical stimuli such as changes in membrane tension during osmotic stress. These channels act as safety valves preventing cell lysis upon hypoosmotic cell swelling: the channels open under membrane tension to release osmolytes along with water. MscS, consists, beside the transmembrane channel, of a large cytoplasmic domain (CD) that features a balloon-like, water filled chamber opening to the cytoplasm through seven side pores and a small distal pore. The CD is apparently a molecular sieve covering the channel, that optimizes loss of osmolytes during osmoadaptation. Diffusion theory and MD simulations are employed to explore the transport kinetics of Glu- and K+ as representative osmolytes. 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