Title : Biological and structural characterization of glycosylation on
ephrin-A1 , a preferred ligand for
EphA2 receptor tyrosine kinase
Abstract :
- The EphA2 receptor tyrosine kinase is overexpressed in a number of malignancies and is activated by ephrin ligands, most commonly by ephrin-A1
- The crystal structure of the ligand- receptor complex revealed a glycosylation on the Asn-26 of ephrin-A1
- Here we report for the first time the significance of the glycosylation in the biology of EphA2 and ephrin-A1
- Ephrin-A1 was enzymatically deglycosylated, and its activity was evaluated in several assays using glioblastoma (GBM) cells and recombinant EphA2
- We found that deglycosylated ephrin-A1 does not efficiently induce EphA2 receptor internalization and degradation, and does not activate the downstream signaling pathways involved in cell migration and proliferation
- Data obtained by surface plasmon resonance confirms that deglycosylated ephrin-A1 does not bind EphA2 with high affinity
- Mutations in the glycosylation site on ephrin-A1 result in protein aggregation and mislocalization
- Analysis of Eph /ephrin crystal structures reveals an interaction between the ligand's carbohydrates and two residues of EphA2 : Asp-78 and Lys-136
- These findings suggest that the glycosylation on ephrin-A1 plays a critical role in the binding and activation of the EphA2 receptor
Output (sent_index, trigger,
protein,
sugar,
site):
- 2. glycosylation, , -, -, Asn-26
- 4. deglycosylated, , Ephrin-A1, -, -
- 5. deglycosylated, , ephrin-A1, -, -
- 6. deglycosylated, , ephrin-A1, -, -
- 7. glycosylation, , -, -, site
- 8. EphA2, , EphA2, the ligand's carbohydrates, -
- 9. glycosylation, , ephrin-A1, -, -
Output(Part-Of) (sent_index,
protein,
site):
- 2. ephrin-A1, Asn-26
- 7. ephrin-A1, site
- 8. EphA2, Asp-78 and Lys-136
- 8. EphA2, residues
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):