| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Outline of Final Research Achievements |
Tyrosylprotein sulfotransferases (TPSTs) are enzymes that catalyse post-translational tyrosine sulfation of proteins and membrane proteins located in the trans Golgi network. In humans, there are two TPST isoforms, designated hTPST1 and hTPST2. We reported the crystal structure of hTPST2. In this research project, we focused on the crystal structure of hTPST1 complexed with two substrate peptides that are catalysed by hTPST1 with significantly different efficiencies. hTPST1 appeared to recognize the substrate peptide in a deep cleft by using a short parallel β-sheet type interaction, and the bound peptide forms an L-shaped structure in the same way as hTPST2.
We knocked down TPST isoform genes in zebrafish and analyzed the effects of TPST deficiency on morphological development. TPST2 knockdown zebrafish resulted in a bent body trunk phenotype, and triple TPST knockdown led to lethal. These suggest that TPST plays an important role during zebrafish development.
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