1fq9
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The crystal structure of a dimeric 2:2:2 FGF:FGFR:heparin ternary complex | + | 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== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Eliseenkova, A | + | [[Category: Eliseenkova, A V.]] |
| - | [[Category: Ibrahimi, O | + | [[Category: Ibrahimi, O A.]] |
| - | [[Category: Linhardt, R | + | [[Category: Linhardt, R J.]] |
[[Category: Mohammadi, M.]] | [[Category: Mohammadi, M.]] | ||
| - | [[Category: Plotnikov, A | + | [[Category: Plotnikov, A N.]] |
[[Category: Schlessinger, J.]] | [[Category: Schlessinger, J.]] | ||
[[Category: Yayon, A.]] | [[Category: Yayon, A.]] | ||
| - | [[Category: Yeh, B | + | [[Category: Yeh, B K.]] |
[[Category: b-trefoil fold]] | [[Category: b-trefoil fold]] | ||
[[Category: i-set subgroup within the immunoglobulin superfamily]] | [[Category: i-set subgroup within the immunoglobulin superfamily]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:41:28 2008'' |
Revision as of 10:41, 21 February 2008
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CRYSTAL STRUCTURE OF A TERNARY FGF2-FGFR1-HEPARIN COMPLEX
Contents |
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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