Dimerization effect of sucrose octasulfate on rat FGF1.
Fibroblast growth factors (FGFs) constitute a family of at least 23 structurally related heparin-binding proteins that are involved in regulation of cell growth, survival, differentiation and migration. Sucrose octasulfate (SOS), a chemical analogue of heparin, has been demonstrated to activate FGF signalling pathways. The structure of rat FGF1 crystallized in the presence of SOS has been determined at 2.2 A resolution. SOS-mediated dimerization of FGF1 was observed, which was further supported by gel-filtration experiments. The major contributors to the sulfate-binding sites in rat FGF1 are Lys113, Lys118, Arg122 and Lys128. An arginine at position 116 is a consensus residue in mammalian FGF molecules; however, it is a serine in rat FGF1. This difference may be important for SOS-mediated FGF1 dimerization in rat.
Protein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark. kulahin@plab.ku.dk
N
N
Kulahin
V
V
Kiselyov
A
A
Kochoyan
O
O
Kristensen
Jette S
JS
Kastrup
V
V
Berezin
E
E
Bock
M
M
Gajhede
D000818:Animals; D000897:Anti-Ulcer Agents / Q000737:chemistry*; D001665:Binding Sites; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D018076:DNA, Complementary; D019281:Dimerization; D004926:Escherichia coli / Q000235:genetics; D016220:Fibroblast Growth Factor 1 / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008970:Molecular Weight; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D013395:Sucrose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
D000897:Anti-Ulcer Agents; D018076:DNA, Complementary; D016220:Fibroblast Growth Factor 1; D013395:Sucrose; C053081:sucrose octasulfate