| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
Growing number of structures are available for the integral membrane proteins. Especially G protein coupled receptors (GPCRs) are the major family encoded by mammalian genomes and extracellular surfaces of them are diversified and are specific for the respective ligands. While several bacterial and algal paralog proteins of GPCR have the other functions such as channels or pumps, no proteins are found as a seven transmembrane (7-TM) enzyme. Here our team performed first attempts to adapt the 7-TM frameworks to enzymes. Point mutations are done for the two residues of the agonist-binding site of the A2a adenosine receptor and then subtle changes in the affinities for the agonist are observed compared with the intact protein. Together, efforts are also focused on the preparation of GPCRs to visualize the resultant 7-TM catalysts. Through the trials of four other class A GPCRs, we have developed the methodology for large-scale preparations, stability analyses, and crystallizations.
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