The G2S Core is the programmatic foundation and resource center of the CMPD project and activities occur at Argonne National Laboratory beamline GMCA and TSRI. G2S is staffed with an experienced team of senior scientists and full-time research technicians with a significant history of successful collaborations which led to the publication of three human GPCR structures in the past 19 months (see Figure 3 in the overall summary), namely Raymond Stevens and a team of Co-Core Directors including Drs. Ellen Chien, Vadim Cherezov and Robert Fischetti. The research is conducted at facilities at TSRI in La Jolla, California and GM/CA-CAT/APS at Argonne, Illinois. In addition, key collaborations are established with Pat Griffin at TSRI-Florida on HDX analysis of membrane proteins and So Iwata at Kyoto University and Imperial College on crystallization with antibodies (see letters of collaboration). G2S will be provided with targets that have been prioritized by Projects 1 and 3 and be responsible for gene construct design and synthesis, expression, purification, and sample characterization, crystallization, and data collection and processing. Methods of sample characterization to be employed in this core include the traditional size exclusion chromatography and gel electrophoresis, as well as the more specialized diffusion and stability analysis by LCP-FRAP, CPM and LCP-Tm, respectively. The highly purified samples that are produced will be evaluated within the Core by crystallographic and NMR methods for structure determination and analysis. Final structure refinement and results dissemination will be coordinated through Projects 1 and 3.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54GM094618-05
Application #
8716778
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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Ngo, Tony; Kufareva, Irina; Coleman, James L J et al. (2016) Identifying ligands at orphan GPCRs: current status using structure-based approaches. Br J Pharmacol :
Kufareva, Irina; Gustavsson, Martin; Holden, Lauren G et al. (2016) Disulfide Trapping for Modeling and Structure Determination of Receptor: Chemokine Complexes. Methods Enzymol 570:389-420
Yang, Dehua; de Graaf, Chris; Yang, Linlin et al. (2016) Structural Determinants of Binding the Seven-transmembrane Domain of the Glucagon-like Peptide-1 Receptor (GLP-1R). J Biol Chem 291:12991-3004
Zheng, Yi; Qin, Ling; Zacarías, Natalia V Ortiz et al. (2016) Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists. Nature 540:458-461
Zhu, Lan; Weierstall, Uwe; Cherezov, Vadim et al. (2016) Serial Femtosecond Crystallography of Membrane Proteins. Adv Exp Med Biol 922:151-60
White, Thomas A; Barty, Anton; Liu, Wei et al. (2016) Serial femtosecond crystallography datasets from G protein-coupled receptors. Sci Data 3:160057
Batyuk, Alexander; Galli, Lorenzo; Ishchenko, Andrii et al. (2016) Native phasing of x-ray free-electron laser data for a G protein-coupled receptor. Sci Adv 2:e1600292
Leach, Katie; Gregory, Karen J; Kufareva, Irina et al. (2016) Towards a structural understanding of allosteric drugs at the human calcium-sensing receptor. Cell Res 26:574-92

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