1fq9

From Proteopedia

Revision as of 14:49, 12 November 2007

CRYSTAL STRUCTURE OF A TERNARY FGF2-FGFR1-HEPARIN COMPLEX

Overview

The crystal structure of a dimeric 2:2:2 FGF:FGFR:heparin ternary complex, at 3 A resolution has been determined. Within each 1:1 FGF:FGFR complex, heparin makes numerous contacts with both FGF and FGFR, thereby augmenting, FGF-FGFR binding. Heparin also interacts with FGFR in the adjoining 1:1, FGF:FGFR complex to promote FGFR dimerization. The 6-O-sulfate group of, heparin plays a pivotal role in mediating both interactions. The, unexpected stoichiometry of heparin binding in the structure led us to, propose a revised model for FGFR dimerization. Biochemical data in support, of this model are also presented. This model provides a structural basis, for FGFR activation by small molecule heparin analogs and may facilitate, the design of heparin mimetics capable of modulating FGF signaling.

Disease

Known diseases associated with this structure: Atopic dermatitis, susceptibility to OMIM:[135940], Hypophosphatemic rickets, autosomal dominant OMIM:[605380], Ichthyosis vulgaris OMIM:[135940], Jackson-Weiss syndrome OMIM:[136350], Kallmann syndrome 2 OMIM:[136350], Osteomalacia, tumor-induced OMIM:[605380], Pfeiffer syndrome OMIM:[136350], Tumoral calcinosis, hyperphosphatemic, familial OMIM:[605380]

About this Structure

1FQ9 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization., Schlessinger J, Plotnikov AN, Ibrahimi OA, Eliseenkova AV, Yeh BK, Yayon A, Linhardt RJ, Mohammadi M, Mol Cell. 2000 Sep;6(3):743-50. PMID:11030354

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