Formation of Proton Translocating Water Channels in ATP Synthase

Maric, Sladjana 1980-

Formation of Proton Translocating Water Channels in ATP Synthase

dc.contributor.advisor	Briggs, James M.
dc.contributor.committeeMember	Bassler, Kevin E.
dc.contributor.committeeMember	Gunaratne, Gemunu H.
dc.contributor.committeeMember	Stokes, Donna W.
dc.creator	Maric, Sladjana 1980-
dc.creator.orcid	0000-0002-0187-1145
dc.date.accessioned	2019-11-07T04:08:51Z
dc.date.created	August 2019
dc.date.issued	2019-08
dc.date.submitted	August 2019
dc.date.updated	2019-11-07T04:08:52Z
dc.description.abstract	The F1FO – ATP synthase has been the object of study in the scientific community both from theory and experiment over the past couple of decades. The ATP synthase is a protein complex in the mitochondrial membrane that efficiently converts the cell’s transmembrane proton gradient into chemical energy stored as adenosine triphosphate (ATP). The protein is made of two molecular motors, F1 and FO, coupled by the central stalk. The free energy used for the synthesis of ATP is in the form of protons moving down the electrochemical gradient from the inner-membrane space to the mitochondrial matrix via the two offset half-channels. The membrane bound part of ATP synthase, FO, converts the transmembrane electrochemical potential into mechanical rotation of the rotor in FO and the stalk physically connected to it. Mutations in a gene encoding ATP synthase are proven to affect its function and cause severe syndromes related to energy deficiency. In this dissertation, we study, using molecular dynamics (MD) simulations, the formation of the half-channels within the stator part of FO. These half-channels enable the proton translocation to and from the rotor portion, known as the c-ring. Combining MD with the protein structure network paths and hydrogen-bonding network analysis, we were able to observe clear evidence for proton pathways and compare our results with previous experimental results. We also report studies of leucine-arginine and leucine-proline amino acid replacements, encoded by the T-G and T-C point mutations at locus 8993 of mtDNA. Our results suggest, for the first time, that these mutations adversely affect water half-channels, and consequently impair the ability of the ATP synthase to produce ATP.
dc.description.department	Physics, Department of
dc.format.digitalOrigin	born digital
dc.format.mimetype	application/pdf
dc.identifier.uri	https://hdl.handle.net/10657/5315
dc.language.iso	eng
dc.rights	The author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subject	F1Fo ATP synthase
dc.subject	Proton transport
dc.subject	Fo half-channels
dc.subject	MtATP6 mutations
dc.title	Formation of Proton Translocating Water Channels in ATP Synthase
dc.type.dcmi	Text
dc.type.genre	Thesis
local.embargo.lift	2021-08-01
local.embargo.terms	2021-08-01
thesis.degree.college	College of Natural Sciences and Mathematics
thesis.degree.department	Physics
thesis.degree.discipline	Physics
thesis.degree.grantor	University of Houston
thesis.degree.level	Doctoral
thesis.degree.name	Doctor of Philosophy