2016 Fiscal Year Final Research Report
Mechanism of protein tyrosine sulfation in virus entry
| Project/Area Number |
26450130
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Applied biochemistry
|
|---|
| Research Institution | University of Miyazaki |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Keywords | 硫酸転移酵素 / 翻訳後修飾 / チロシン硫酸化 / ゼブラフィッシュ / 遺伝子ノックダウン / モルフォリノアンチセンスオリゴ / X線結晶構造解析 / 構造と活性 |
|---|
| 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.
|
| Free Research Field |
農芸化学・応用生物化学
|
