We have made substantial progress on several of the Specific Aims proposed in 2006 and further focused future directions toward the challenging long-time aim of understanding eukaryotic channel gating by ligands, particularly in the Acetylcholine Receptor (AcChR). A major subtext has always been to attempt to define structures of eukaryotic and human proteins because of their importance for drug discovery. Towards this goal, we determined two of the first four structures for human membrane proteins, using expression in human cultured HEK293S cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
3R37GM024485-37S1
Application #
8846330
Study Section
Program Officer
Chin, Jean
Project Start
1979-04-01
Project End
2016-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
37
Fiscal Year
2014
Total Cost
$32,267
Indirect Cost
$11,845
Name
University of California San Francisco
Department
Biochemistry
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Kintzer, Alexander F; Green, Evan M; Dominik, Pawel K et al. (2018) Structural basis for activation of voltage sensor domains in an ion channel TPC1. Proc Natl Acad Sci U S A 115:E9095-E9104
Kintzer, Alexander F; Stroud, Robert M (2018) On the structure and mechanism of two-pore channels. FEBS J 285:233-243
Boswell-Casteel, Rebba C; Johnson, Jennifer M; Stroud, Robert M et al. (2016) Integral Membrane Protein Expression in Saccharomyces cerevisiae. Methods Mol Biol 1432:163-86
Kapoor, Khyati; Finer-Moore, Janet S; Pedersen, Bjørn P et al. (2016) Mechanism of inhibition of human glucose transporter GLUT1 is conserved between cytochalasin B and phenylalanine amides. Proc Natl Acad Sci U S A 113:4711-6
Thurtle-Schmidt, Bryan H; Stroud, Robert M (2016) Structure of Bor1 supports an elevator transport mechanism for SLC4 anion exchangers. Proc Natl Acad Sci U S A 113:10542-6
Kintzer, Alexander F; Stroud, Robert M (2016) Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana. Nature 531:258-62
Salo-Ahen, Outi M H; Tochowicz, Anna; Pozzi, Cecilia et al. (2015) Hotspots in an obligate homodimeric anticancer target. Structural and functional effects of interfacial mutations in human thymidylate synthase. J Med Chem 58:3572-81
Johri, Atul K; Oelmüller, Ralf; Dua, Meenakshi et al. (2015) Fungal association and utilization of phosphate by plants: success, limitations, and future prospects. Front Microbiol 6:984
Kim, JungMin; Wu, Shenping; Tomasiak, Thomas M et al. (2015) Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter. Nature 517:396-400
Kumar, Hemant; Finer-Moore, Janet S; Kaback, H Ronald et al. (2015) Structure of LacY with an ?-substituted galactoside: Connecting the binding site to the protonation site. Proc Natl Acad Sci U S A 112:9004-9

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