Analysis of putative heparin-binding domains of fibroblast growth factor-1. Using site-directed mutagenesis and peptide analogues.


Abstract

The contribution of individual basic amino acids within three putative "consensus sequences" for heparin binding of fibroblast growth factor-1 have been examined by site-directed mutagenesis. The results indicate that a significant reduction in the apparent affinity of fibroblast growth factor-1 for heparin is only observed when basic residues in one of the three regions are mutated. Mutation in the other regions are without affect on heparin binding. The heparin binding properties of synthetic peptides based on the three "consensus sequences" paralleled the mutagenesis results. That is, synthetic peptides corresponding to regions of the protein that were affected by mutagenesis with respect to heparin binding exhibited a relatively high affinity for immobilized heparin, whereas those corresponding to regions of similar charge density that were unaffected by mutagenesis did not. In addition, amino acid substitution of a nonbasic residue in the heparin-binding peptide could abolish its heparin binding capacity. The heparin-binding peptide could antagonize the mitogenic activity of FGF-1, probably because of the heparin dependence of this activity. Together these data demonstrate that the heparin binding properties of fibroblast growth factor-1 are dictated by structural features more complex than clusters of basic amino acids. The results of these and other studies indicate that consensus motifs for heparin-binding require further definition. More importantly, the results provide a basis for the design of peptide-based inhibitors of FGF-1.

Submission Details

ID: 2U6eRS4X3

Submitter: Connie Wang

Submission Date: Sept. 28, 2018, 5:19 p.m.

Version: 1

Publication Details
Wong P;Hampton B;Szylobryt E;Gallagher AM;Jaye M;Burgess WH,J Biol Chem (1995) Analysis of putative heparin-binding domains of fibroblast growth factor-1. Using site-directed mutagenesis and peptide analogues. PMID:7592764
Additional Information

Sequence Assay Result Units