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 #
5R37GM024485-37
Application #
8603239
Study Section
Special Emphasis Panel (NSS)
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
$416,084
Indirect Cost
$146,774
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
Kumar, Hemant; Kasho, Vladimir; Smirnova, Irina et al. (2014) Structure of sugar-bound LacY. Proc Natl Acad Sci U S A 111:1784-8
Monk, Brian C; Tomasiak, Thomas M; Keniya, Mikhail V et al. (2014) Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer. Proc Natl Acad Sci U S A 111:3865-70
Pedersen, Bjorn P; Kumar, Hemant; Waight, Andrew B et al. (2013) Crystal structure of a eukaryotic phosphate transporter. Nature 496:533-6
Pak, John Edward; Ekende, Elisabeth Ngonlong; Kifle, Efrem G et al. (2013) Structures of intermediate transport states of ZneA, a Zn(II)/proton antiporter. Proc Natl Acad Sci U S A 110:18484-9
Chaudhary, Sarika; Pak, John E; Gruswitz, Franz et al. (2012) Overexpressing human membrane proteins in stably transfected and clonal human embryonic kidney 293S cells. Nat Protoc 7:453-66
Savage, David F; O'Connell 3rd, Joseph D; Miercke, Larry J W et al. (2010) Structural context shapes the aquaporin selectivity filter. Proc Natl Acad Sci U S A 107:17164-9
Lee, John Kyongwon; Stroud, Robert Michael (2010) Unlocking the eukaryotic membrane protein structural proteome. Curr Opin Struct Biol 20:464-70
Ho, Joseph D; Yeh, Ronald; Sandstrom, Andrew et al. (2009) Crystal structure of human aquaporin 4 at 1.8 A and its mechanism of conductance. Proc Natl Acad Sci U S A 106:7437-42
Newby, Zachary E R; O'Connell 3rd, Joseph; Robles-Colmenares, Yaneth et al. (2008) Crystal structure of the aquaglyceroporin PfAQP from the malarial parasite Plasmodium falciparum. Nat Struct Mol Biol 15:619-25
Savage, David F; Stroud, Robert M (2007) Structural basis of aquaporin inhibition by mercury. J Mol Biol 368:607-17

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