title: Investigating the mechanism of the assembly of FGF1-binding heparan sulfate motifs.
abstract: Heparan sulfate (HS) chains play crucial biological roles by binding to various signaling molecules including fibroblast growth factors (FGFs). Distinct sulfation patterns of HS chains are required for their binding to FGFs/FGF receptors (FGFRs). These sulfation patterns are putatively regulated by biosynthetic enzyme complexes, called GAGOSOMES, in the Golgi. While the structural requirements of HS-FGF interactions have been described previously, it is still unclear how the FGF-binding motif is assembled in vivo. In this study, we generated HS structures using biosynthetic enzymes in a sequential or concurrent manner to elucidate the potential mechanism by which the FGF1-binding HS motif is assembled. Our results indicate that the HS chains form ternary complexes with FGF1/FGFR when enzymes carry out modifications in a specific manner.
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Thao Kim Nu
authors.initials: TK
authors.lastname: Nguyen
authors.forename: Karthik
authors.initials: K
authors.lastname: Raman
authors.forename: Vy My
authors.initials: VM
authors.lastname: Tran
authors.forename: Balagurunathan
authors.initials: B
authors.lastname: Kuberan
mesh_terms: D002240:Carbohydrate Sequence; D024202:Electrophoretic Mobility Shift Assay; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry / Q000378:metabolism*; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism
chemical_list: D016220:Fibroblast Growth Factor 1; D006497:Heparan Sulfate; D011134:Polysaccharides; D017468:Receptors, Fibroblast Growth Factor