The long-term goal of this project is to gain an understanding on the structure/function relationship of the ATP synthase as it relates to mechanism of the ATP synthase. Recently, in a collaborative study, we were able to obtain a 3.2-3.3 A map of the yeast F1 ATPase. This major advance now allows us to ask and answer questions using the full tools of yeast genetics and x-ray crystallography. The studies in this proposal, in part, investigate the molecular impact of mutations in genes encoding subunits of the mitochondrial ATP synthase on the structure and function of the ATP synthase.
In first aim of this study, the crystal structure analysis will be completed and improved to even further resolution.
The second aim will use both site directed and random mutagenesis to investigate the structure/function relationship of the interactions of the gamma-subunit.
The third aim will investigate the role of nucleotide binding on forming the active sites of the enzyme, F1F0 ATP synthase.
This final aim represents the most ambitious aim of the 4, but also represents the single most important remaining goal needed in the understanding of the mechanism of the mitochondrial ATP synthase. These experiments will provide a further understanding on the structure function of the ATP synthase, but will also provide important information on the functional consequences of mutations in subunits of he ATP synthase. Ultimately, this project will provide critical information on the regulation of the ATP synthase and the importance of this regulation on the overall capabilities of the cell to provide enough energy as demanded by tissue and organism in both the normal and disease state.
| Srivastava, Anurag P; Luo, Min; Zhou, Wenchang et al. (2018) High-resolution cryo-EM analysis of the yeast ATP synthase in a lipid membrane. Science 360: |
| Xu, Ting; Pagadala, Vijayakanth; Mueller, David M (2015) Understanding structure, function, and mutations in the mitochondrial ATP synthase. Microb Cell 2:105-125 |
| Steel, Bradley C; Nord, Ashley L; Wang, Yamin et al. (2015) Comparison between single-molecule and X-ray crystallography data on yeast F1-ATPase. Sci Rep 5:8773 |
| Shah, Kalpit; Cheng, Yi; Hahn, Brian et al. (2015) Synonymous codon usage affects the expression of wild type and F508del CFTR. J Mol Biol 427:1464-1479 |
| Lieber, Daniel S; Calvo, Sarah E; Shanahan, Kristy et al. (2013) Targeted exome sequencing of suspected mitochondrial disorders. Neurology 80:1762-70 |
| Robinson, Graham C; Bason, John V; Montgomery, Martin G et al. (2013) The structure of F?-ATPase from Saccharomyces cerevisiae inhibited by its regulatory protein IF?. Open Biol 3:120164 |
| Bilyard, Thomas; Nakanishi-Matsui, Mayumi; Steel, Bradley C et al. (2013) High-resolution single-molecule characterization of the enzymatic states in Escherichia coli F1-ATPase. Philos Trans R Soc Lond B Biol Sci 368:20120023 |
| Symersky, Jindrich; Osowski, Daniel; Walters, D Eric et al. (2012) Oligomycin frames a common drug-binding site in the ATP synthase. Proc Natl Acad Sci U S A 109:13961-5 |
| Symersky, Jindrich; Pagadala, Vijayakanth; Osowski, Daniel et al. (2012) Structure of the c(10) ring of the yeast mitochondrial ATP synthase in the open conformation. Nat Struct Mol Biol 19:485-91, S1 |
| Pagadala, Vijayakanth; Vistain, Luke; Symersky, Jindrich et al. (2011) Characterization of the mitochondrial ATP synthase from yeast Saccharomyces cerevisae. J Bioenerg Biomembr 43:333-47 |
Showing the most recent 10 out of 21 publications
