A cationic motif in Engrailed-2 homeoprotein controls its internalization via selective cell-surface glycosaminoglycans interactions - Archive ouverte HAL Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2021

A cationic motif in Engrailed-2 homeoprotein controls its internalization via selective cell-surface glycosaminoglycans interactions

Sébastien Cardon
  • Fonction : Auteur
Gérard Bolbach
  • Fonction : Auteur
Yadira Hervis
Chrystel Lopin-Bon
Jean-Claude Jacquinet
Delphine Ravault
Bingwei He
  • Fonction : Auteur
Laura Molina
Olivier Lequin
Alain Joliot
Ludovic Carlier

Résumé

Abstract 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.

Dates et versions

hal-03429466 , version 1 (15-11-2021)

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Sébastien Cardon, Gérard Bolbach, Yadira Hervis, Chrystel Lopin-Bon, Jean-Claude Jacquinet, et al.. A cationic motif in Engrailed-2 homeoprotein controls its internalization via selective cell-surface glycosaminoglycans interactions. 2021. ⟨hal-03429466⟩

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