A cationic motif in Engrailed-2 homeoprotein controls its internalization via selective cell-surface glycosaminoglycans interactions
| Autor: | Alain Joliot, Astrid Walrant, Françoise Illien, Sandrine Sagan, Olivier Lequin, Gérard Bolbach, Fabienne Burlina, Jean-Claude Jacquinet, Delphine Ravault, Laura Molina, Yadira P. Hervis, Bingwei He, Sébastien Cardon, Ludovic Carlier, Chrystel Lopin-Bon |
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| Přispěvatelé: | Sorbonne Université (SU) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
0303 health sciences media_common.quotation_subject [SDV]Life Sciences [q-bio] Cell Heparan sulfate engrailed Amino acid Cell biology Glycosaminoglycan 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine.anatomical_structure chemistry medicine [CHIM]Chemical Sciences Internalization Transcription factor 030217 neurology & neurosurgery Binding selectivity 030304 developmental biology media_common |
| Popis: | Engrailed-2 (En2) is a transcription factor that possesses as most homeoproteins the unique and intriguing property to transfer from cell to cell through unconventional pathways. The internalization mechanism of this cationic protein is far from being fully understood and is proposed to require an initial interaction with cell-surface glycosaminoglycans (GAGs). To decipher the role of GAGs in the recognition of En2 at the cell surface, we have quantified the internalization of the homeodomain region in cell lines that differ in their content in cell-surface GAGs. The binding specificity to GAGs and the influence of this interaction on the structure and dynamics of En2 was also investigated at the amino acid level. Our results show that a high-affinity GAG-binding hexadecapeptide (RKPKKKNPNKEDKRPR) located upstream of the homeodomain controls internalization efficiency of En2 through selective interactions with highly-sulfated GAGs of heparan sulfate type. Our data underline the functional importance of the intrinsically disordered basic region that precedes the prominent internalization domain in En2, and demonstrate the critical role of GAGs as an entry gate for En2, finely tuning its capacity to internalize into cells. |
| Databáze: | OpenAIRE |
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