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Function and dynamics of rotor-stator interactions in the proton-translocating Fo motor of ATP synthase

Award Number: R15GM134453
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY F1Fo ATP synthase is a fundamental energy conversion complex found in all known cells. This complex uses an electrochemical gradient of ions to drive a rotary mechanism that results in the synthesis of adenosine triphosphate (ATP), the universal chemical energy currency of life. In E. coli, the proton-driven Fo motor, embedded in the cell membrane, consists of a decameric subunit c rotor ring in contact with subunit a of the stator. Protons move through Fo via two offset aqueous half channels. Protons enter through subunit a from the periplasm (P-side) to the c-ring. After c-ring rotation, protons exit to the cytoplasm (N-side) by a half channel formed at the a-c interface. Clusters of residues along the N-side channel have been implicated in proton translocation and a possible gating mechanism, but the roles of these residues are unclear. This project seeks to engage undergraduate student researchers in a combined biochemical and biophysical approach to characterize interactions between the rotor and stator and establish their role(s) in proton transport. Aim 1 will systematically examine mutations and chemical modifications of several key residues on the N-side of the a-c interface with a battery of in vitro biochemical assays to determine the role of each residue in proton-driven ATP synthesis and ATP-driven proton pumping. Aim 2 will use site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy to probe the structure and structural dynamics of the loop regions of subunit a that interact with the c-ring. Patterns of spin label mobility, accessibility, and proximity will reveal whether interacting cytoplasmic loops at the a-c interface undergo conformational changes during ATP synthesis or hydrolysis. Together, the structural and functional data will contribute to understanding the molecular mechanism of proton transport in this important biomolecular machine and inform future drug development.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$2,090 )
2024	2019	THE UNIVERSITY OF NORTH CAROLINA AT ASHEVILLE	1 UNIVERSITY HEIGHTS	ASHEVILLE	NC	28804	BUNCOMBE	USA	Biomedical Research and Research Training	000	1	1/11/2024	NEW	-$2,090
														Subtotal = -$2,090

Issue Date FY: 2019 ( Subtotal = $326,674 )
2019	2019	UNIVERSITY OF NORTH CAROLINA AT ASHEVILLE, THE	ONE UNIVERSITY HEIGHTS	ASHEVILLE	NC	28804	BUNCOMBE	USA	Biomedical Research and Research Training	000	1	7/31/2019	NEW	$326,674
														Subtotal = $326,674

Grand Total All Awards = $324,584

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Function and dynamics of rotor-stator interactions in the proton-translocating Fo motor of ATP synthase

Award Number: R15GM134453

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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