2AXM

HEPARIN-LINKED BIOLOGICALLY-ACTIVE DIMER OF FIBROBLAST GROWTH FACTOR

Summary for 2AXM

• Entry DOI: 10.2210/pdb2axm/pdb
• Descriptor: ACIDIC FIBROBLAST GROWTH FACTOR, 2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose (3 entities in total)
• Functional Keywords: human acidic fibroblast growth factor, heparin decasaccharide, hexagonal crystal form, growth factor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 32328.83

Authors

Digabriele, A.D.,Lax, I.,Chen, D.I.,Svahn, C.M.,Jaye, M.,Schlessinger, J.,Hendrickson, W.A. (deposition date: 1997-10-20, release date: 1998-04-22, Last modification date: 2024-05-22)

Primary citation

DiGabriele, A.D.,Lax, I.,Chen, D.I.,Svahn, C.M.,Jaye, M.,Schlessinger, J.,Hendrickson, W.A.
Structure of a heparin-linked biologically active dimer of fibroblast growth factor.
Nature, 393:812-817, 1998

PubMed Abstract: The fibroblast growth factors (FGFs) form a large family of structurally related, multifunctional proteins that regulate various biological responses. They mediate cellular functions by binding to transmembrane FGF receptors, which are protein tyrosine kinases. FGF receptors are activated by oligomerization, and both this activation and FGF-stimulated biological responses require heparin-like molecules as well as FGF. Heparins are linear anionic polysaccharide chains; they are typically heterogeneously sulphated on alternating L-iduronic and D-glucosamino sugars, and are nearly ubiquitous in animal tissues as heparan sulphate proteoglycans on cell surfaces and in the extracellular matrix. Although several crystal structures have been described for FGF molecules in complexes with heparin-like sugars, the nature of a biologically active complex has been unknown until now. Here we describe the X-ray crystal structure, at 2.9 A resolution, of a biologically active dimer of human acidic FGF in a complex with a fully sulphated, homogeneous heparin decassacharide. The dimerization of heparin-linked acidic FGF observed here is an elegant mechanism for the modulation of signalling through combinatorial homodimerization and heterodimerization of the 12 known members of the FGF family.

PubMed: 9655399
DOI: 10.1038/31741

Experimental method

X-RAY DIFFRACTION (3 Å)