| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
The functional regulation and conformational regulation of growth factor receptors ErbB by N-glycans were examined. N-glycans on EGFR N420, ErbB3 N418, ErbB4 N333 were involved in receptor activation. We examined the site-specific glycosylation status and glycan structures of ErbBs and found that their glycan occupancies were 100% and they were a complex type with little fucose. The signaling inhibitory effects were increased in sEGFR N420Q and sErbB3 N418Q mutants. Although the crystal structure of sErbB3 was not altered by the deletion of N-glycan on N418 by N418Q mutation, the melting temperature of sErbB3 N418Q decreased compared to the wild type, suggesting that this N-glycan contributes to the conformational stability of sErbB3. Taken together, our results suggested that N-glycan on N418 of sErbB3 is involved in the stabilization of structure and that deletion of this glycan increases the structural flexibility which results in facilitation of dimer formation.
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