title: Secondary conformational conversion is involved in glycosaminoglycans-mediated cellular uptake of the cationic cell-penetrating peptide PACAP.
abstract: Glycosaminoglycans (GAGs) contribute to the cellular uptake of cationic cell-penetrating peptides (CPPs). However, molecular details about the contributions of GAGs in CPP internalization remain unclear. In this study, we examined the cellular uptake mechanism of the arginine-rich CPP pituitary adenylate-cyclase-activating polypeptide (PACAP). We observed that the uptake efficacy of PACAP is dependent on the expression of cell surface GAGs. As the binding of PACAP to sulfated GAGs induced a random coil-to-α-helix conformational conversion, we investigated the role of the helical formation in PACAP internalization. Whereas this secondary structure was not crucial for efficient internalization in GAGs-deficient cells, PACAP α-helix was essential for GAGs-dependent uptake.
authors.affiliation: Department of Chemistry, Pharmaqam, University of Québec in Montreal, Montreal, QC H3C 3P8, Canada; Quebec Network for Research on Protein Function, Structure, and Engineering, PROTEO, Canada.
authors.forename: Armelle
authors.initials: A
authors.lastname: Tchoumi Neree
authors.affiliation: Department of Chemistry, Pharmaqam, University of Québec in Montreal, Montreal, QC H3C 3P8, Canada; Quebec Network for Research on Protein Function, Structure, and Engineering, PROTEO, Canada.
authors.forename: Phuong Trang
authors.initials: PT
authors.lastname: Nguyen
authors.affiliation: INRS-Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC H7V 1B7, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Chatenet
authors.affiliation: INRS-Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC H7V 1B7, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.affiliation: Department of Chemistry, Pharmaqam, University of Québec in Montreal, Montreal, QC H3C 3P8, Canada; Quebec Network for Research on Protein Function, Structure, and Engineering, PROTEO, Canada. Electronic address: bourgault.steve@uqam.ca.
authors.forename: Steve
authors.initials: S
authors.lastname: Bourgault
mesh_terms: D000327:Adsorption; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis; D006025:Glycosaminoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D008969:Molecular Sequence Data; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary
chemical_list: D057846:Cell-Penetrating Peptides; D006025:Glycosaminoglycans; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D006493:Heparin
keywords: Cell-penetrating peptide; Cellular uptake; Glycosaminoglycan; Pituitary adenylate cyclase-activating polypeptide; α-Helix