A cationic motif upstream Engrailed2 homeodomain controls cell internalization through selective interaction with heparan sulfates - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2023

A cationic motif upstream Engrailed2 homeodomain controls cell internalization through selective interaction with heparan sulfates

Yadira Hervis
Olivier Lequin

Résumé

Engrailed2 (En2) is a transcription factor that transfers from cell to cell through unconventional pathways. The poorly understood internalization mechanism of this cationic protein is proposed to require an initial interaction with cell-surface glycosaminoglycans (GAGs). To decipher the role of GAGs in En2 internalization, we have quantified the entry of its homeodomain region in model cells 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 sequence (RKPKKKNPNKEDKRPR), upstream of the homeodomain, controls En2 internalization through selective interactions with highly-sulfated heparan sulfate GAGs. Our data underline the functional importance of the intrinsically disordered basic region upstream of En2 internalization domain, and demonstrate the critical role of GAGs as an entry gate, finely tuning homeoprotein capacity to internalize into cells.
Fichier principal
Vignette du fichier
Cardon_Nat Comm_2023.pdf (1.84 Mo) Télécharger le fichier
Cardon_Suppl Information_2023.pdf (9.72 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Origine : Publication financée par une institution

Dates et versions

hal-04263695 , version 1 (30-10-2023)

Identifiants

Citer

Sébastien Cardon, Yadira Hervis, Gérard Bolbach, Chrystel Lopin-Bon, Jean-Claude Jacquinet, et al.. A cationic motif upstream Engrailed2 homeodomain controls cell internalization through selective interaction with heparan sulfates. Nature Communications, 2023, 14 (1), pp.1998. ⟨10.1038/s41467-023-37757-6⟩. ⟨hal-04263695⟩

Relations

66 Consultations
9 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More