The structural investigation of glycosaminoglycan binding to CXCL12 displays distinct interaction sites

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Nydia Panitz - , Universität Leipzig (Erstautor:in)
  • Stephan Theisgen - , Universität Leipzig (Autor:in)
  • Sergey A Samsonov - , Strukturelle Bioinformatik (FoG), Biotechnologisches Zentrum (BIOTEC) (Autor:in)
  • Jan-Philip Gehrcke - , Biotechnologisches Zentrum (BIOTEC) (Autor:in)
  • Lars Baumann - , Universität Leipzig (Autor:in)
  • Kathrin Bellmann-Sickert - , Universität Leipzig (Autor:in)
  • Sebastian Köhling - , Freie Universität (FU) Berlin (Autor:in)
  • M Teresa Pisabarro - , Strukturelle Bioinformatik (FoG), Biotechnologisches Zentrum (BIOTEC) (Autor:in)
  • Jörg Rademann - , Freie Universität (FU) Berlin (Autor:in)
  • Daniel Huster - , Universität Leipzig (Autor:in)
  • Annette G Beck-Sickinger - , Universität Leipzig (Autor:in)

Abstract

The stromal cell-derived factor 1α (CXCL12) belongs to the CXC chemokine family and plays an important role in tissue regeneration and the recruitment of stem cells. Here, a stable chemotactic gradient is essential that is formed by the interaction of CXCL12 with the extracellular matrix. Binding properties of CXCL12 to naturally occurring glycosaminoglycans (GAGs) as well as to the artificial highly sulfated hyaluronic acid (HA) are investigated by using a combination of NMR spectroscopy, molecular modeling and molecular dynamics simulations. Our results demonstrate a preferred protein binding for the sulfated GAGs heparin (HE) and highly sulfated HA. Furthermore, we could demonstrate that the orientation of the sulfate is crucial for binding. All sulfated GAGs interact with the CXCL12 GAG-binding motif (K24-H25-L26-K27-R41-K43-R47), where K27 and R41 represent the anchor points. Furthermore, differences could be observed in the second interaction interface of CXCL12: both HE and highly sulfated HA interfere with the receptor-binding motif, while chondroitin sulfate binds different amino acids in close proximity to this motif. CXCL12 does not interact with HA, which was directly demonstrated by NMR spectroscopy and molecular modeling and explained by the lack of sulfate groups of the HA molecule.

Details

OriginalspracheEnglisch
Seiten (von - bis)1209-1221
Seitenumfang13
FachzeitschriftGlycobiology
Jahrgang26
Ausgabenummer11
PublikationsstatusVeröffentlicht - Nov. 2016
Peer-Review-StatusJa

Externe IDs

Scopus 85016237451

Schlagworte

Schlagwörter

  • Binding Sites, Carbohydrate Conformation, Chemokine CXCL12/chemistry, Glycosaminoglycans/chemistry, Humans, Models, Molecular

Bibliotheksschlagworte