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Structural Constraint of Osteopontin Facilitates Efficient Binding to CD44.
Fnu, Gulimirerouzi; Agrawal, Palak; Kundu, Gopal C; Weber, Georg F.
Afiliação
  • Fnu G; College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH 45229, USA.
  • Agrawal P; National Centre for Cell Science, Pune 411007, Maharashtra, India.
  • Kundu GC; National Centre for Cell Science, Pune 411007, Maharashtra, India.
  • Weber GF; College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH 45229, USA.
Biomolecules ; 11(6)2021 05 30.
Article em En | MEDLINE | ID: mdl-34070790
ABSTRACT
Since the original description in 1996, the interaction between the cytokine osteopontin (OPN) and the homing receptor CD44 has been extensively studied in cancer, inflammation, bone remodeling, and various other conditions. Alternative splicing and extensive posttranslational modifications by both binding partners, as well as the possibility for lateral recruitment of additional membrane receptors or soluble co-ligands into a complex have left the exact molecular requirements for high-affinity OPN-CD44 binding unresolved. We now report that there is a moderate engagement between the unmodified molecules, which results in curved double-reciprocal plots for OPN titration, suggesting the existence of two binding sites or two binding conformations. Structural constraint of OPN, by immobilization or by addition of heparin, is required for its strong ligation of CD44. Prior literature provides evidence that heparin binding to OPN prompts the unfolding of a core element in the protein. This conformational adjustment may be essential for efficient CD44 interaction. The integrin α9ß1 seems to compete with the OPN-CD44 engagement, while the integrin αVß3 reflects additive binding, suggesting that the CD44 contact sites on OPN are downstream of the RGD motif but overlap with the SVVYGLR domain. Hyaluronate has no effect, placing the relevant domain on CD44 downstream of the N-terminus.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de Hialuronatos / Osteopontina Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de Hialuronatos / Osteopontina Idioma: En Ano de publicação: 2021 Tipo de documento: Article